Hassane S. Mchaourab, Ph.D.

Professor

hassane.mchaourab@vanderbilt.edu

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Faculty Appointments
Professor of Molecular Physiology and Biophysics Louise B. McGavock ChairProfessor of Chemistry
Education
Ph.D., Molecular Physiology and Biophysics, Medical College of Wisconsin, Milwaukee, WisconsinM.S., American University of Beirut, Beirut, LebanonB.S., American University of Beirut, Beirut, Lebanon
Office Address
741 Light Hall
Nashville, TN 0615
Research Description
Research in the Mchaourab Laboratory is focused on understanding the structural and dynamic basis of protein function with focus on proteins that are involved in diseases. Using spectroscopic approaches, our laboratory studies the molecular aspect of: protein aggregation diseases such as cataract, the widespread phenomenon of multidrug resistance in cancer and infectious diseases and more recently neurotransmitter transport across the synaptic cleft in collaboration with Aurelio Galli’s Laboratory.

Lens aging, protein folding and Cataract: Small heat-shock proteins, including the major protein component in the lens alpha-crystallin, are molecular chaperones that help other proteins avoid aggregation. Protein aggregation is associated with many pathogenic conditions including alzheimer's diseases, mad cow disease and cataract. Our laboratory has pioneered novel assay to understand the mechanisms of both inherited and age-related cataract. We investigate small heat-shock proteins from various organisms and across the evolutionary spectrum.

Multidrug resistance in Cancer: Active drug extrusion by multidrug transporters is one of four general mechanisms associated with the multidrug resistance phenomenon, a key problem in the treatment of bacterial and fungal infections and cancers. The overexpression of adenosine triphosphate binding cassette (ABC) transporters is the most frequent cause of resistance to cytotoxic agents. In addition, mutations in the genes encoding the 48 human ABC transporters are associated with diseases such as cystic fibrosis, Tangier disease and adrenoleukodystrophy. Our laboratory is investigating how these transporters work, a key step in the design of therapeutic strategies.

Neurotransmitter transport: Chemical synapses are junctions at which electrical signals are relayed from one neuron to another via release of neurotransmitters such as dopamine, serotonin and norepinephrine. The process of clearing these molecules controls the magnitude and duration of synaptic signaling. Neurotransmitter transporters are integral membrane proteins that move neurotransmitter back into the neuronal terminal thus terminating signaling. In collaboration with the Galli laboratory at Vanderbilt, we are investigating the process of transport as well as its modulation by kinases. A future goal is to determine the structural basis of antidepressants, amphetamine and cocaine effects on the properties of these transporters.
Research Keywords
Eye Lens Proteins, Heat Shock Proteins, neurotransmitter transporters, Multidrug transporters, structural biology, Spectroscopy,
Publications
Collauto A, Mishra S, Litvinov A, Mchaourab HS, Goldfarb D. Direct Spectroscopic Detection of ATP Turnover Reveals Mechanistic Divergence of ABC Exporters. Structure [print-electronic]. 2017 Aug 8/1/2017; 25(8): 1264-1274.e3. PMID: 28712805, PII: S0969-2126(17)30194-6, DOI: 10.1016/j.str.2017.06.014, ISSN: 1878-4186.

Carra S, Alberti S, Arrigo PA, Benesch JL, Benjamin IJ, Boelens W, Bartelt-Kirbach B, Brundel BJJM, Buchner J, Bukau B, Carver JA, Ecroyd H, Emanuelsson C, Finet S, Golenhofen N, Goloubinoff P, Gusev N, Haslbeck M, Hightower LE, Kampinga HH, Klevit RE, Liberek K, Mchaourab HS, McMenimen KA, Poletti A, Quinlan R, Strelkov SV, Toth ME, Vierling E, Tanguay RM. The growing world of small heat shock proteins: from structure to functions. Cell Stress Chaperones [print-electronic]. 2017 Jul; 22(4): 601-11. PMID: 28364346, PMCID: PMC5465036, PII: 10.1007/s12192-017-0787-8, DOI: 10.1007/s12192-017-0787-8, ISSN: 1466-1268.

Verhalen B, Dastvan R, Thangapandian S, Peskova Y, Koteiche HA, Nakamoto RK, Tajkhorshid E, Mchaourab HS. Energy transduction and alternating access of the mammalian ABC transporter P-glycoprotein. Nature [print-electronic]. 2017 Mar 3/30/2017; 543(7647): 738-41. PMID: 28289287, PMCID: PMC5558441, PII: nature21414, DOI: 10.1038/nature21414, ISSN: 1476-4687.

Kazmier K, Claxton DP, Mchaourab HS. Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes. Curr. Opin. Struct. Biol [print-electronic]. 2016 Dec 12/29/2016; 45: 100-8. PMID: 28040635, PMCID: PMC5491374, PII: S0959-440X(16)30171-3, DOI: 10.1016/j.sbi.2016.12.006, ISSN: 1879-033X.

Wu SY, Zou P, Fuller AW, Mishra S, Wang Z, Schey KL, Mchaourab HS. Expression of Cataract-linked ¿-Crystallin Variants in Zebrafish Reveals a Proteostasis Network That Senses Protein Stability. J. Biol. Chem [print-electronic]. 2016 Dec 12/2/2016; 291(49): 25387-97. PMID: 27770023, PMCID: PMC5207241, PII: M116.749606, DOI: 10.1074/jbc.M116.749606, ISSN: 1083-351X.

Martens C, Stein RA, Masureel M, Roth A, Mishra S, Dawaliby R, Konijnenberg A, Sobott F, Govaerts C, Mchaourab HS. Lipids modulate the conformational dynamics of a secondary multidrug transporter. Nat. Struct. Mol. Biol [print-electronic]. 2016 Aug; 23(8): 744-51. PMID: 27399258, PMCID: PMC5248563, PII: nsmb.3262, DOI: 10.1038/nsmb.3262, ISSN: 1545-9985.

Zhu S, Stein RA, Yoshioka C, Lee CH, Goehring A, Mchaourab HS, Gouaux E. Mechanism of NMDA Receptor Inhibition and Activation. Cell [print-electronic]. 2016 Apr 4/21/2016; 165(3): 704-14. PMID: 27062927, PMCID: PMC4914038, PII: S0092-8674(16)30326-9, DOI: 10.1016/j.cell.2016.03.028, ISSN: 1097-4172.

Arrigoni C, Rohaim A, Shaya D, Findeisen F, Stein RA, Nurva SR, Mishra S, Mchaourab HS, Minor DL. Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation. Cell. 2016 Feb 2/25/2016; 164(5): 922-36. PMID: 26919429, PMCID: PMC4769381, PII: S0092-8674(16)30067-8, DOI: 10.1016/j.cell.2016.02.001, ISSN: 1097-4172.

Dastvan R, Fischer AW, Mishra S, Meiler J, Mchaourab HS. Protonation-dependent conformational dynamics of the multidrug transporter EmrE. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2016 Feb 2/2/2016; 113(5): 1220-5. PMID: 26787875, PMCID: PMC4747756, PII: 1520431113, DOI: 10.1073/pnas.1520431113, ISSN: 1091-6490.

Khantwal CM, Abraham SJ, Han W, Jiang T, Chavan TS, Cheng RC, Elvington SM, Liu CW, Mathews II, Stein RA, Mchaourab HS, Tajkhorshid E, Maduke M. Revealing an outward-facing open conformational state in a CLC Cl(-)/H(+) exchange transporter. Elife. 2016 Jan 1/22/2016; 5: PMID: 26799336, PMCID: PMC4769167, DOI: 10.7554/eLife.11189, ISSN: 2050-084X.

Krug U, Alexander NS, Stein RA, Keim A, Mchaourab HS, Sträter N, Meiler J. Characterization of the Domain Orientations of E. coli 5'-Nucleotidase by Fitting an Ensemble of Conformers to DEER Distance Distributions. Structure [print-electronic]. 2016 Jan 1/5/2016; 24(1): 43-56. PMID: 26724996, PMCID: PMC4706771, PII: S0969-2126(15)00496-7, DOI: 10.1016/j.str.2015.11.007, ISSN: 1878-4186.

Mori T, Mchaourab H, Johnson CH. Circadian Clocks: Unexpected Biochemical Cogs. Curr. Biol. 2015 Oct 10/5/2015; 25(19): R842-4. PMID: 26439342, PMCID: PMC4697453, PII: S0960-9822(15)00997-5, DOI: 10.1016/j.cub.2015.08.026, ISSN: 1879-0445.

Schmandt N, Velisetty P, Chalamalasetti SV, Stein RA, Bonner R, Talley L, Parker MD, Mchaourab HS, Yee VC, Lodowski DT, Chakrapani S. A chimeric prokaryotic pentameric ligand-gated channel reveals distinct pathways of activation. J. Gen. Physiol. 2015 Oct; 146(4): 323-40. PMID: 26415570, PMCID: PMC4586589, PII: jgp.201511478, DOI: 10.1085/jgp.201511478, ISSN: 1540-7748.

Koteiche HA, Claxton DP, Mishra S, Stein RA, McDonald ET, Mchaourab HS. Species-Specific Structural and Functional Divergence of a-Crystallins: Zebrafish aBa- and Rodent aA(ins)-Crystallin Encode Activated Chaperones. Biochemistry [print-electronic]. 2015 Sep 9/29/2015; 54(38): 5949-58. PMID: 26378715, PMCID: PMC5240591, DOI: 10.1021/acs.biochem.5b00678, ISSN: 1520-4995.

Kaur H, Lakatos A, Spadaccini R, Vogel R, Hoffmann C, Becker-Baldus J, Ouari O, Tordo P, Mchaourab H, Glaubitz C. The ABC exporter MsbA probed by solid state NMR – challenges and opportunities. Biol. Chem. 2015 Sep; 396(9-10): 1135-49. PMID: 25849794, PII: /j/bchm.just-accepted/hsz-2015-0119/hsz-2015-0119.xml, DOI: 10.1515/hsz-2015-0119, ISSN: 1437-4315.

Zou P, Wu SY, Koteiche HA, Mishra S, Levic DS, Knapik E, Chen W, Mchaourab HS. A conserved role of aA-crystallin in the development of the zebrafish embryonic lens. Exp. Eye Res [print-electronic]. 2015 Sep; 138: 104-13. PMID: 26149094, PMCID: PMC4638411, PII: S0014-4835(15)00220-1, DOI: 10.1016/j.exer.2015.07.001, ISSN: 1096-0007.

Meyer V, Swanson MA, Clouston LJ, Boratynski PJ, Stein RA, Mchaourab HS, Rajca A, Eaton SS, Eaton GR. Room-temperature distance measurements of immobilized spin-labeled protein by DEER/PELDOR. Biophys. J. 2015 Mar 3/10/2015; 108(5): 1213-9. PMID: 25762332, PMCID: PMC4375670, PII: S0006-3495(15)00078-8, DOI: 10.1016/j.bpj.2015.01.015, ISSN: 1542-0086.

Anderson DM, Floyd KA, Barnes S, Clark JM, Clark JI, Mchaourab H, Schey KL. A method to prevent protein delocalization in imaging mass spectrometry of non-adherent tissues: application to small vertebrate lens imaging. Anal Bioanal Chem [print-electronic]. 2015 Mar; 407(8): 2311-20. PMID: 25665708, PMCID: PMC4379205, DOI: 10.1007/s00216-015-8489-5, ISSN: 1618-2650.

Claxton DP, Kazmier K, Mishra S, Mchaourab HS. Navigating Membrane Protein Structure, Dynamics, and Energy Landscapes Using Spin Labeling and EPR Spectroscopy. Meth. Enzymol [print-electronic]. 2015; 564: 349-87. PMID: 26477257, PMCID: PMC5222538, PII: S0076-6879(15)00430-9, DOI: 10.1016/bs.mie.2015.07.026, ISSN: 1557-7988.

Kazmier K, Sharma S, Islam SM, Roux B, Mchaourab HS. Conformational cycle and ion-coupling mechanism of the Na+/hydantoin transporter Mhp1. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2014 Oct 10/14/2014; 111(41): 14752-7. PMID: 25267652, PMCID: PMC4205665, PII: 1410431111, DOI: 10.1073/pnas.1410431111, ISSN: 1091-6490.

Yu Z, Quine RW, Rinard GA, Tseitlin M, Elajaili H, Kathirvelu V, Clouston LJ, Boratynski PJ, Rajca A, Stein R, Mchaourab H, Eaton SS, Eaton GR. Rapid-scan EPR of immobilized nitroxides. J. Magn. Reson [print-electronic]. 2014 Oct; 247: 67-71. PMID: 25240151, PMCID: PMC4247172, PII: S1090-7807(14)00221-3, DOI: 10.1016/j.jmr.2014.08.008, ISSN: 1096-0856.

Dürr KL, Chen L, Stein RA, De Zorzi R, Folea IM, Walz T, Mchaourab HS, Gouaux E. Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states. Cell [print-electronic]. 2014 Aug 8/14/2014; 158(4): 778-92. PMID: 25109876, PMCID: PMC4263325, PII: S0092-8674(14)00937-4, DOI: 10.1016/j.cell.2014.07.023, ISSN: 1097-4172.

Mishra S, Verhalen B, Stein RA, Wen PC, Tajkhorshid E, Mchaourab HS. Conformational dynamics of the nucleotide binding domains and the power stroke of a heterodimeric ABC transporter. Elife. 2014 May 5/16/2014; 3: e02740. PMID: 24837547, PMCID: PMC4046567, DOI: 10.7554/eLife.02740, ISSN: 2050-084X.

Kazmier K, Sharma S, Quick M, Islam SM, Roux B, Weinstein H, Javitch JA, McHaourab HS. Conformational dynamics of ligand-dependent alternating access in LeuT. Nat. Struct. Mol. Biol [print-electronic]. 2014 May; 21(5): 472-9. PMID: 24747939, PMCID: PMC4050370, PII: nsmb.2816, DOI: 10.1038/nsmb.2816, ISSN: 1545-9985.

Masureel M, Martens C, Stein RA, Mishra S, Ruysschaert JM, Mchaourab HS, Govaerts C. Protonation drives the conformational switch in the multidrug transporter LmrP. Nat. Chem. Biol [print-electronic]. 2014 Feb; 10(2): 149-55. PMID: 24316739, PMCID: PMC4749020, PII: nchembio.1408, DOI: 10.1038/nchembio.1408, ISSN: 1552-4469.

Hamilton PJ, Campbell NG, Sharma S, Erreger K, Herborg Hansen F, Saunders C, Belovich AN, , Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A. De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder. Mol. Psychiatry [print-electronic]. 2013 Dec; 18(12): 1315-23. PMID: 23979605, PMCID: PMC4046646, PII: mp2013102, DOI: 10.1038/mp.2013.102, ISSN: 1476-5578.

Hamilton PJ, Campbell NG, Sharma S, Erreger K, Hansen FH, Saunders C, Belovich AN, Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A. Drosophila melanogaster: a novel animal model for the behavioral characterization of autism-associated mutations in the dopamine transporter gene. Mol. Psychiatry. 2013 Dec; 18(12): 1235. PMID: 24253181, PII: mp2013157, DOI: 10.1038/mp.2013.157, ISSN: 1476-5578.

Steed PR, Zou P, Trone KE, Mchaourab HS. Structure and pH-induced structural rearrangements of the putative multidrug efflux pump EmrD in liposomes probed by site-directed spin labeling. Biochemistry [print-electronic]. 2013 Nov 11/12/2013; 52(45): 7964-74. PMID: 24148002, PMCID: PMC3855667, DOI: 10.1021/bi4012385, ISSN: 1520-4995.

Steed PR, Stein RA, Mishra S, Goodman MC, McHaourab HS. Na¿-substrate coupling in the multidrug antiporter norm probed with a spin-labeled substrate. Biochemistry [print-electronic]. 2013 Aug 8/27/2013; 52(34): 5790-9. PMID: 23902581, PMCID: PMC3842230, DOI: 10.1021/bi4008935, ISSN: 1520-4995.

Wen PC, Verhalen B, Wilkens S, Mchaourab HS, Tajkhorshid E. On the origin of large flexibility of P-glycoprotein in the inward-facing state. J. Biol. Chem [print-electronic]. 2013 Jun 6/28/2013; 288(26): 19211-20. PMID: 23658020, PMCID: PMC3696692, PII: M113.450114, DOI: 10.1074/jbc.M113.450114, ISSN: 1083-351X.

Islam SM, Stein RA, McHaourab HS, Roux B. Structural refinement from restrained-ensemble simulations based on EPR/DEER data: application to T4 lysozyme. J Phys Chem B [print-electronic]. 2013 May 5/2/2013; 117(17): 4740-54. PMID: 23510103, PMCID: PMC3684008, DOI: 10.1021/jp311723a, ISSN: 1520-5207.

Shi J, Koteiche HA, McDonald ET, Fox TL, Stewart PL, McHaourab HS. Cryoelectron microscopy analysis of small heat shock protein 16.5 (Hsp16.5) complexes with T4 lysozyme reveals the structural basis of multimode binding. J. Biol. Chem [print-electronic]. 2013 Feb 2/15/2013; 288(7): 4819-30. PMID: 23277356, PMCID: PMC3576087, PII: M112.388132, DOI: 10.1074/jbc.M112.388132, ISSN: 1083-351X.

Alexander NS, Stein RA, Koteiche HA, Kaufmann KW, McHaourab HS, Meiler J. RosettaEPR: rotamer library for spin label structure and dynamics. PLoS ONE. 2013; 8(9): e72851. PMID: 24039810, PMCID: PMC3764097, PII: PONE-D-13-07728, DOI: 10.1371/journal.pone.0072851, ISSN: 1932-6203.

Yirdaw RB, McHaourab HS. Direct observation of T4 lysozyme hinge-bending motion by fluorescence correlation spectroscopy. Biophys. J [print-electronic]. 2012 Oct 10/3/2012; 103(7): 1525-36. PMID: 23062345, PMCID: PMC3471472, PII: S0006-3495(12)00919-8, DOI: 10.1016/j.bpj.2012.07.053, ISSN: 1542-0086.

McHaourab HS, Lin YL, Spiller BW. Crystal structure of an activated variant of small heat shock protein Hsp16.5. Biochemistry [print-electronic]. 2012 Jun 6/26/2012; 51(25): 5105-12. PMID: 22670769, PMCID: PMC3384710, DOI: 10.1021/bi300525x, ISSN: 1520-4995.

Mishra S, Stein RA, McHaourab HS. Cataract-linked ¿D-crystallin mutants have weak affinity to lens chaperones a-crystallins. FEBS Lett [print-electronic]. 2012 Feb 2/17/2012; 586(4): 330-6. PMID: 22289178, PMCID: PMC3282170, PII: S0014-5793(12)00052-X, DOI: 10.1016/j.febslet.2012.01.019, ISSN: 1873-3468.

McDonald ET, Bortolus M, Koteiche HA, Mchaourab HS. Sequence, structure, and dynamic determinants of Hsp27 (HspB1) equilibrium dissociation are encoded by the N-terminal domain. Biochemistry [print-electronic]. 2012 Feb 2/14/2012; 51(6): 1257-68. PMID: 22264079, PMCID: PMC3293247, DOI: 10.1021/bi2017624, ISSN: 1520-4995.

McHaourab HS, Steed PR, Kazmier K. Toward the fourth dimension of membrane protein structure: insight into dynamics from spin-labeling EPR spectroscopy. Structure. 2011 Nov 11/9/2011; 19(11): 1549-61. PMID: 22078555, PMCID: PMC3224804, PII: S0969-2126(11)00363-7, DOI: 10.1016/j.str.2011.10.009, ISSN: 1878-4186.

Mushrush DJ, Koteiche HA, Sammons MA, Link AJ, McHaourab HS, Lacy DB. Studies of the mechanistic details of the pH-dependent association of botulinum neurotoxin with membranes. J. Biol. Chem [print-electronic]. 2011 Jul 7/29/2011; 286(30): 27011-8. PMID: 21652698, PMCID: PMC3143659, PII: M111.256982, DOI: 10.1074/jbc.M111.256982, ISSN: 1083-351X.

Hoffman L, Stein RA, Colbran RJ, Mchaourab HS. Conformational changes underlying calcium/calmodulin-dependent protein kinase II activation. EMBO J [print-electronic]. 2011 Apr 4/6/2011; 30(7): 1251-62. PMID: 21343908, PMCID: PMC3094114, PII: emboj201140, DOI: 10.1038/emboj.2011.40, ISSN: 1460-2075.

Kazmier K, Alexander NS, Meiler J, McHaourab HS. Algorithm for selection of optimized EPR distance restraints for de novo protein structure determination. J. Struct. Biol [print-electronic]. 2011 Mar; 173(3): 549-57. PMID: 21074624, PMCID: PMC3073550, PII: S1047-8477(10)00340-0, DOI: 10.1016/j.jsb.2010.11.003, ISSN: 1095-8657.

Hirst SJ, Alexander N, McHaourab HS, Meiler J. RosettaEPR: an integrated tool for protein structure determination from sparse EPR data. J. Struct. Biol [print-electronic]. 2011 Mar; 173(3): 506-14. PMID: 21029778, PMCID: PMC3040274, PII: S1047-8477(10)00333-3, DOI: 10.1016/j.jsb.2010.10.013, ISSN: 1095-8657.

Amadi ST, Koteiche HA, Mishra S, McHaourab HS. Structure, dynamics, and substrate-induced conformational changes of the multidrug transporter EmrE in liposomes. J. Biol. Chem [print-electronic]. 2010 Aug 8/20/2010; 285(34): 26710-8. PMID: 20551331, PMCID: PMC2924113, PII: M110.132621, DOI: 10.1074/jbc.M110.132621, ISSN: 1083-351X.

Qin X, Byrne M, Mori T, Zou P, Williams DR, McHaourab H, Johnson CH. Intermolecular associations determine the dynamics of the circadian KaiABC oscillator. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Aug 8/17/2010; 107(33): 14805-10. PMID: 20679240, PMCID: PMC2930409, PII: 1002119107, DOI: 10.1073/pnas.1002119107, ISSN: 1091-6490.

Claxton DP, Quick M, Shi L, de Carvalho FD, Weinstein H, Javitch JA, McHaourab HS. Ion/substrate-dependent conformational dynamics of a bacterial homolog of neurotransmitter:sodium symporters. Nat. Struct. Mol. Biol [print-electronic]. 2010 Jul; 17(7): 822-9. PMID: 20562855, PMCID: PMC3245867, PII: nsmb.1854, DOI: 10.1038/nsmb.1854, ISSN: 1545-9985.

Gustot A, Smriti, Ruysschaert JM, McHaourab H, Govaerts C. Lipid composition regulates the orientation of transmembrane helices in HorA, an ABC multidrug transporter. J. Biol. Chem [print-electronic]. 2010 May 5/7/2010; 285(19): 14144-51. PMID: 20223819, PMCID: PMC2863179, PII: M109.079673, DOI: 10.1074/jbc.M109.079673, ISSN: 1083-351X.

Zou P, McHaourab HS. Increased sensitivity and extended range of distance measurements in spin-labeled membrane proteins: Q-band double electron-electron resonance and nanoscale bilayers. Biophys. J. 2010 Mar 3/17/2010; 98(6): L18-20. PMID: 20303847, PMCID: PMC2849076, PII: S0006-3495(09)06005-6, DOI: 10.1016/j.bpj.2009.12.4193, ISSN: 1542-0086.

Zou P, McHaourab HS. Alternating access of the putative substrate-binding chamber in the ABC transporter MsbA. J. Mol. Biol [print-electronic]. 2009 Oct 10/30/2009; 393(3): 574-85. PMID: 19715704, PMCID: PMC2760602, PII: S0022-2836(09)01060-2, DOI: 10.1016/j.jmb.2009.08.051, ISSN: 1089-8638.

Zou P, Bortolus M, McHaourab HS. Conformational cycle of the ABC transporter MsbA in liposomes: detailed analysis using double electron-electron resonance spectroscopy. J. Mol. Biol [print-electronic]. 2009 Oct 10/30/2009; 393(3): 586-97. PMID: 19715702, PMCID: PMC2760609, PII: S0022-2836(09)01059-6, DOI: 10.1016/j.jmb.2009.08.050, ISSN: 1089-8638.

Smriti, Zou P, McHaourab HS. Mapping daunorubicin-binding Sites in the ATP-binding cassette transporter MsbA using site-specific quenching by spin labels. J. Biol. Chem [print-electronic]. 2009 May 5/15/2009; 284(20): 13904-13. PMID: 19278995, PMCID: PMC2679490, PII: M900837200, DOI: 10.1074/jbc.M900837200, ISSN: 0021-9258.

McHaourab HS, Godar JA, Stewart PL. Structure and mechanism of protein stability sensors: chaperone activity of small heat shock proteins. Biochemistry. 2009 May 5/12/2009; 48(18): 3828-37. PMID: 19323523, PMCID: PMC2785012, DOI: 10.1021/bi900212j, ISSN: 1520-4995.

Latham JC, Stein RA, Bornhop DJ, Mchaourab HS. Free-solution label-free detection of alpha-crystallin chaperone interactions by back-scattering interferometry. Anal. Chem. 2009 Mar 3/1/2009; 81(5): 1865-71. PMID: 19178288, PMCID: PMC2787765, PII: 10.1021/ac802327h, DOI: 10.1021/ac802327h, ISSN: 1520-6882.

Kumar MS, Koteiche HA, Claxton DP, Mchaourab HS. Disulfide cross-links in the interaction of a cataract-linked alphaA-crystallin mutant with betaB1-crystallin. FEBS Lett [print-electronic]. 2009 Jan 1/5/2009; 583(1): 175-9. PMID: 19071118, PII: S0014-5793(08)00963-0, DOI: 10.1016/j.febslet.2008.11.047, ISSN: 1873-3468.

McHaourab HS, Mishra S, Koteiche HA, Amadi SH. Role of sequence bias in the topology of the multidrug transporter EmrE. Biochemistry [print-electronic]. 2008 Aug 8/5/2008; 47(31): 7980-2. PMID: 18616286, DOI: 10.1021/bi800628d, ISSN: 1520-4995.

Alexander N, Bortolus M, Al-Mestarihi A, Mchaourab H, Meiler J. De novo high-resolution protein structure determination from sparse spin-labeling EPR data. Structure. 2008 Feb; 16(2): 181-95. PMID: 18275810, PMCID: PMC2390841, PII: S0969-2126(08)00012-9, DOI: 10.1016/j.str.2007.11.015, ISSN: 0969-2126.

Claxton DP, Zou P, Mchaourab HS. Structure and orientation of T4 lysozyme bound to the small heat shock protein alpha-crystallin. J. Mol. Biol [print-electronic]. 2008 Jan 1/25/2008; 375(4): 1026-39. PMID: 18062989, PMCID: PMC2276617, PII: S0022-2836(07)01474-X, DOI: 10.1016/j.jmb.2007.11.014, ISSN: 1089-8638.

Cobb NJ, Sönnichsen FD, McHaourab H, Surewicz WK. Molecular architecture of human prion protein amyloid: a parallel, in-register beta-structure. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Nov 11/27/2007; 104(48): 18946-51. PMID: 18025469, PMCID: PMC2141888, PII: 0706522104, DOI: 10.1073/pnas.0706522104, ISSN: 1091-6490.

Borbat PP, Surendhran K, Bortolus M, Zou P, Freed JH, Mchaourab HS. Conformational motion of the ABC transporter MsbA induced by ATP hydrolysis. PLoS Biol. 2007 Oct; 5(10): e271. PMID: 17927448, PMCID: PMC2001213, PII: 07-PLBI-RA-1117, DOI: 10.1371/journal.pbio.0050271, ISSN: 1545-7885.

McHaourab HS, Kumar MS, Koteiche HA. Specificity of alphaA-crystallin binding to destabilized mutants of betaB1-crystallin. FEBS Lett [print-electronic]. 2007 May 5/15/2007; 581(10): 1939-43. PMID: 17449033, PMCID: PMC2219212, PII: S0014-5793(07)00379-1, DOI: 10.1016/j.febslet.2007.04.005, ISSN: 0014-5793.

Koteiche HA, Kumar MS, McHaourab HS. Analysis of betaB1-crystallin unfolding equilibrium by spin and fluorescence labeling: evidence of a dimeric intermediate. FEBS Lett [print-electronic]. 2007 May 5/15/2007; 581(10): 1933-8. PMID: 17448466, PMCID: PMC2394508, PII: S0014-5793(07)00378-X, DOI: 10.1016/j.febslet.2007.04.004, ISSN: 0014-5793.

Mori T, Williams DR, Byrne MO, Qin X, Egli M, Mchaourab HS, Stewart PL, Johnson CH. Elucidating the ticking of an in vitro circadian clockwork. PLoS Biol. 2007 Apr; 5(4): e93. PMID: 17388688, PMCID: PMC1831719, PII: 06-PLBI-RA-2188R2, DOI: 10.1371/journal.pbio.0050093, ISSN: 1545-7885.

Zou P, Surendhran K, Mchaourab HS. Distance measurements by fluorescence energy homotransfer: evaluation in T4 lysozyme and correlation with dipolar coupling between spin labels. Biophys. J [print-electronic]. 2007 Feb 2/15/2007; 92(4): L27-9. PMID: 17142264, PMCID: PMC1783887, PII: S0006-3495(07)70918-9, DOI: 10.1529/biophysj.106.098913, ISSN: 0006-3495.

Shi J, Koteiche HA, McHaourab HS, Stewart PL. Cryoelectron microscopy and EPR analysis of engineered symmetric and polydisperse Hsp16.5 assemblies reveals determinants of polydispersity and substrate binding. J. Biol. Chem [print-electronic]. 2006 Dec 12/29/2006; 281(52): 40420-8. PMID: 17079234, PII: M608322200, DOI: 10.1074/jbc.M608322200, ISSN: 0021-9258.

Koteiche HA, Mchaourab HS. Mechanism of a hereditary cataract phenotype. Mutations in alphaA-crystallin activate substrate binding. J. Biol. Chem [print-electronic]. 2006 May 5/19/2006; 281(20): 14273-9. PMID: 16531622, PII: M512938200, DOI: 10.1074/jbc.M512938200, ISSN: 0021-9258.

Altenbach C, Froncisz W, Hemker R, McHaourab H, Hubbell WL. Accessibility of nitroxide side chains: absolute Heisenberg exchange rates from power saturation EPR. Biophys. J [print-electronic]. 2005 Sep; 89(3): 2103-12. PMID: 15994891, PMCID: PMC1366712, PII: S0006-3495(05)72854-X, DOI: 10.1529/biophysj.105.059063, ISSN: 0006-3495.

Koteiche HA, Chiu S, Majdoch RL, Stewart PL, Mchaourab HS. Atomic models by cryo-EM and site-directed spin labeling: application to the N-terminal region of Hsp16.5. Structure. 2005 Aug; 13(8): 1165-71. PMID: 16084388, PII: S0969-2126(05)00206-6, DOI: 10.1016/j.str.2005.05.006, ISSN: 0969-2126.

Dong J, Yang G, McHaourab HS. Structural basis of energy transduction in the transport cycle of MsbA. Science. 2005 May 5/13/2005; 308(5724): 1023-8. PMID: 15890883, PII: 308/5724/1023, DOI: 10.1126/science.1106592, ISSN: 1095-9203.

Shashidharamurthy R, Koteiche HA, Dong J, McHaourab HS. Mechanism of chaperone function in small heat shock proteins: dissociation of the HSP27 oligomer is required for recognition and binding of destabilized T4 lysozyme. J. Biol. Chem [print-electronic]. 2005 Feb 2/18/2005; 280(7): 5281-9. PMID: 15542604, PII: M407236200, DOI: 10.1074/jbc.M407236200, ISSN: 0021-9258.

Sathish HA, Koteiche HA, McHaourab HS. Binding of destabilized betaB2-crystallin mutants to alpha-crystallin: the role of a folding intermediate. J. Biol. Chem [print-electronic]. 2004 Apr 4/16/2004; 279(16): 16425-32. PMID: 14761939, PII: M313402200, DOI: 10.1074/jbc.M313402200, ISSN: 0021-9258.

Sathish HA, Stein RA, Yang G, Mchaourab HS. Mechanism of chaperone function in small heat-shock proteins. Fluorescence studies of the conformations of T4 lysozyme bound to alphaB-crystallin. J. Biol. Chem [print-electronic]. 2003 Nov 11/7/2003; 278(45): 44214-21. PMID: 12928430, PII: M307578200, DOI: 10.1074/jbc.M307578200, ISSN: 0021-9258.

Koteiche HA, Reeves MD, McHaourab HS. Structure of the substrate binding pocket of the multidrug transporter EmrE: site-directed spin labeling of transmembrane segment 1. Biochemistry. 2003 May 5/27/2003; 42(20): 6099-105. PMID: 12755611, DOI: 10.1021/bi0342867, ISSN: 0006-2960.

Koteiche HA, McHaourab HS. Mechanism of chaperone function in small heat-shock proteins. Phosphorylation-induced activation of two-mode binding in alphaB-crystallin. J. Biol. Chem [print-electronic]. 2003 Mar 3/21/2003; 278(12): 10361-7. PMID: 12529319, PII: M211851200, DOI: 10.1074/jbc.M211851200, ISSN: 0021-9258.

Mchaourab HS, Dodson EK, Koteiche HA. Mechanism of chaperone function in small heat shock proteins. Two-mode binding of the excited states of T4 lysozyme mutants by alphaA-crystallin. J. Biol. Chem [print-electronic]. 2002 Oct 10/25/2002; 277(43): 40557-66. PMID: 12189146, PII: M206250200, DOI: 10.1074/jbc.M206250200, ISSN: 0021-9258.

Koteiche HA, Mchaourab HS. The determinants of the oligomeric structure in Hsp16.5 are encoded in the alpha-crystallin domain. FEBS Lett. 2002 May 5/22/2002; 519(1-3): 16-22. PMID: 12023011, PII: S0014579302026881, ISSN: 0014-5793.

Borbat PP, McHaourab HS, Freed JH. Protein structure determination using long-distance constraints from double-quantum coherence ESR: study of T4 lysozyme. J. Am. Chem. Soc. 2002 May 5/15/2002; 124(19): 5304-14. PMID: 11996571, PII: ja020040y, ISSN: 0002-7863.

Mansoor SE, McHaourab HS, Farrens DL. Mapping proximity within proteins using fluorescence spectroscopy. A study of T4 lysozyme showing that tryptophan residues quench bimane fluorescence. Biochemistry. 2002 Feb 2/26/2002; 41(8): 2475-84. PMID: 11851393, PII: bi011198i, ISSN: 0006-2960.

Kaplan RS, Mayor JA, Kotaria R, Walters DE, McHaourab HS. The yeast mitochondrial citrate transport protein: determination of secondary structure and solvent accessibility of transmembrane domain IV using site-directed spin labeling. Biochemistry. 2000 Aug 8/8/2000; 39(31): 9157-63. PMID: 10924109, PII: bi000433e, ISSN: 0006-2960.

Haley DA, Bova MP, Huang QL, Mchaourab HS, Stewart PL. Small heat-shock protein structures reveal a continuum from symmetric to variable assemblies. J. Mol. Biol. 2000 Apr 4/28/2000; 298(2): 261-72. PMID: 10764595, PII: S0022-2836(00)93657-X, DOI: 10.1006/jmbi.2000.3657, ISSN: 0022-2836.

Bova MP, McHaourab HS, Han Y, Fung BK. Subunit exchange of small heat shock proteins. Analysis of oligomer formation of alphaA-crystallin and Hsp27 by fluorescence resonance energy transfer and site-directed truncations. J. Biol. Chem. 2000 Jan 1/14/2000; 275(2): 1035-42. PMID: 10625643, ISSN: 0021-9258.

Haley DA, Bova MP, Huang QL, Mchaourab HS, and Stewart PL. Small heat-shock protein structures reveal a continuum from symmetric to variable assemblies. J. Mol. Biol. 2000; 298: 261-72.

Bova MP, Mchaourab HS, Han Y, and Fung BK. Subunit exchange of small heat-shock proteins. Analysis of oligomer formation of A-crystallin and Hsp27 by Fluorescence energy transfer and site-directed truncations. J. Biol. Chem. 2000; 275: 1035-42.

Kaplan RS, Mayor JA, Kotaria R, Walters DE, and Mchaourab HS. The yeast mitochondrial citrate transport protein: determination of secondary structure and solvent accessibility of transmembrane domain IV using site-directed spin labeling. Biochemistry. 2000; 39: 9157-63.

Mansoor SE, McHaourab HS, Farrens DL. Determination of protein secondary structure and solvent accessibility using site-directed fluorescence labeling. Studies of T4 lysozyme using the fluorescent probe monobromobimane. Biochemistry. 1999 Dec 12/7/1999; 38(49): 16383-93. PMID: 10587464, PII: bi991331v, ISSN: 0006-2960.

Koteiche HA, Mchaourab HS. Folding pattern of the alpha-crystallin domain in alphaA-crystallin determined by site-directed spin labeling. J. Mol. Biol. 1999 Nov 11/26/1999; 294(2): 561-77. PMID: 10610780, PII: S0022-2836(99)93242-4, DOI: 10.1006/jmbi.1999.3242, ISSN: 0022-2836.

Barnes JP, Liang Z, Mchaourab HS, Freed JH, Hubbell WL. A multifrequency electron spin resonance study of T4 lysozyme dynamics. Biophys. J. 1999 Jun; 76(6): 3298-306. PMID: 10354455, PMCID: PMC1300299, PII: S0006-3495(99)77482-5, DOI: 10.1016/S0006-3495(99)77482-5, ISSN: 0006-3495.

Mchaourab HS, Kálai T, Hideg K, Hubbell WL. Motion of spin-labeled side chains in T4 lysozyme: effect of side chain structure. Biochemistry. 1999 Mar 3/9/1999; 38(10): 2947-55. PMID: 10074347, PII: bi9826310, DOI: 10.1021/bi9826310, ISSN: 0006-2960.

Berengian AR, Parfenova M, Mchaourab HS. Site-directed spin labeling study of subunit interactions in the alpha-crystallin domain of small heat-shock proteins. Comparison of the oligomer symmetry in alphaA-crystallin, HSP 27, and HSP 16.3. J. Biol. Chem. 1999 Mar 3/5/1999; 274(10): 6305-14. PMID: 10037719, ISSN: 0021-9258.

Koteiche HA and Mchaourab HS. Folding pattern of the alpha-crystallin domain determined by site-directed spin labeling. J. Mol. Biol. 1999; 294: 561-77.

Berengian AR, Parfenova M, and Mchaourab HS. Site- directed spin labeling study of subunit interactions in the alpha-crystallin domain of small heat-shock proteins. Comparison of the oligomer symmetry in alphaA-crystallin, HSP27, and HSP16.3. J. Biol. Chem. 1999; 274: 6305-14.

Mansoor SE, Mchaourab HS, ans Farrens DL. Determination of protein secondary structure and solvent accessibility using site-directed fluorescence labeling. Studies of T4 lysozyme using the fluorescent probe monobromobimane. Biochemistry. 1999; 38: 16383-93.

Mchaourab HS, Kálai T, Hideg K, and Hubbell WL. Motion of spin labeled side chains in T4 lysozyme: effect of side chain structure. Biochemistry. 1999; 38: 2947 55.

Barnes JP, Liang Z, Mchaourab HS, Freed JH, and Hubbell WL. A multifrequency electron spin resonance study of T4 lysozyme dynamics. Biophys. J. 1999; 76: 3298-306.

Koteiche HA, Berengian AR, Mchaourab HS. Identification of protein folding patterns using site-directed spin labeling. Structural characterization of a beta-sheet and putative substrate binding regions in the conserved domain of alpha A-crystallin. Biochemistry. 1998 Sep 9/15/1998; 37(37): 12681-8. PMID: 9737844, PII: bi9814078, DOI: 10.1021/bi9814078, ISSN: 0006-2960.

Hyde JS, Mchaourab HS, Camenisch T, Ratke JJ, Cox RW, and Froncisz W. EPR detection by time-locked sub-sampling. Rev. Sci. Instrum. 1998; 69: 2622-8.

Koteiche HA, Berengian AR, and Mchaourab HS. Identification of protein folding patterns using site-directed spin labeling. Structural characterization of a -sheet and putative substrate binding regions in the conserved domain of A-crystallin. Biochemistry. 1998; 37: 126821-12688.

Mchaourab HS, Berengian AR, Koteiche HA. Site-directed spin-labeling study of the structure and subunit interactions along a conserved sequence in the alpha-crystallin domain of heat-shock protein 27. Evidence of a conserved subunit interface. Biochemistry. 1997 Dec 12/2/1997; 36(48): 14627-34. PMID: 9398181, PII: bi971700s, DOI: 10.1021/bi971700s, ISSN: 0006-2960.

Berengian AR, Bova MP, Mchaourab HS. Structure and function of the conserved domain in alphaA-crystallin. Site-directed spin labeling identifies a beta-strand located near a subunit interface. Biochemistry. 1997 Aug 8/19/1997; 36(33): 9951-7. PMID: 9296605, PII: bi9712347, DOI: 10.1021/bi9712347, ISSN: 0006-2960.

Mchaourab HS, Oh KJ, Fang CJ, Hubbell WL. Conformation of T4 lysozyme in solution. Hinge-bending motion and the substrate-induced conformational transition studied by site-directed spin labeling. Biochemistry. 1997 Jan 1/14/1997; 36(2): 307-16. PMID: 9003182, PII: bi962114m, DOI: 10.1021/bi962114m, ISSN: 0006-2960.

Mchaourab HS, Oh KJ, Fang CJ, and Hubbell WL. The conformation of T4 lysozyme in solution. Hinge bending motion and the substrate-induced conformational transition studied by site-directed spin labeling. Biochemistry. 1997; 36: 307-16.

Berengian AR, Bova MP, and Mchaourab HS. Structure and function of the conserved domain in A-crystallin. Site-directed spin labeling identifies a -strand located near a subunit interface. Biochemistry. 1997; 36: 9951-7.

Mchaourab HS, Berengian A, and Koteiche HA. Site-directed spin-labeling study of the structure and subunit interactions along a conserved sequence in the -crystallin domain of heat-shock protein 27. Evidence of a conserved subunit interface. Biochemistry. 1997; 36: 14627-34.

Hubbell WL, Mchaourab HS, Altenbach C, Lietzow MA. Watching proteins move using site-directed spin labeling. Structure. 1996 Jul 7/15/1996; 4(7): 779-83. PMID: 8805569, PII: S0969-2126(96)00085-8, ISSN: 0969-2126.

Mchaourab HS, Lietzow MA, Hideg K, Hubbell WL. Motion of spin-labeled side chains in T4 lysozyme. Correlation with protein structure and dynamics. Biochemistry. 1996 Jun 6/18/1996; 35(24): 7692-704. PMID: 8672470, PII: bi960482k, DOI: 10.1021/bi960482k, ISSN: 0006-2960.

Hubbell WL, Mchaourab HS, Altenbach C, and Lietzow M. Watching proteins move using site-directed spin labeling. Structure. 1996; 4: 779-83.

Mchaourab HS, Lietzow MA, Hideg K, and Hubbell WL. Motion of spin-labeled side chains in T4 lysozyme. Correlation with protein structure and dynamics. Biochemistry. 1996; 35: 7692-704.

Singh RJ, Feix JB, Mchaourab HS, Hogg N, Kalyanaraman B. Spin-labeling study of the oxidative damage to low-density lipoprotein. Arch. Biochem. Biophys. 1995 Jun 6/20/1995; 320(1): 155-61. PMID: 7793976, PII: S0003-9861(85)71354-9, DOI: 10.1006/abbi.1995.1354, ISSN: 0003-9861.

Hyde JS, Strangeway RA, Luglio J, Mchaourab HS, and Froncisz W. Noise in EPR bridges with multiple time-locked microwave frequencies. Bull. Magn. Reson. 1995; 17: 54-60.

Strangeway RA, Mchaourab HS, Luglio JR, Froncisz W, and Hyde JS. A general multipurpose multiquantum EPR spectrometer. Rev. Sci. Instrum. 1995; 66: 4516-28.

Singh RJ, Hogg N, Mchaourab HS, and Kalyanaraman B. Physical and chemical interactions between nitric oxide and nitroxides. Biochim. Biophys. Acta. 1995; 1201: 437.

Singh RJ, Feix JB, Mchaourab HS, Hogg N, and Kalyanaraman B. Spin labeling study of the oxidative damage to low-density lipoprotein. Arch. Biochem. Biophys. 1995; 320: 155.

Singh RJ, Hogg N, Mchaourab HS, Kalyanaraman B. Physical and chemical interactions between nitric oxide and nitroxides. Biochim. Biophys. Acta. 1994 Dec 12/15/1994; 1201(3): 437-41. PMID: 7803474, ISSN: 0006-3002.

Mchaourab HS, Hyde JS, Feix JB. Binding and state of aggregation of spin-labeled cecropin AD in phospholipid bilayers: effects of surface charge and fatty acyl chain length. Biochemistry. 1994 May 5/31/1994; 33(21): 6691-9. PMID: 8204604, ISSN: 0006-2960.

Mchaourab HS, Hyde JS, and Feix JB. Binding and state of aggregation of spin-labeled cecropin AD in phospholipid bilayers: effect of surface charge and fatty acyl chain length. Biochemistry. 1994; 33: 6691.

Mchaourab HS, Hyde JS, and Feix JB. Aggregation state of spin-labeled cecropin AD in solution. Biochemistry. 1994; 33: 11895.

Mchaourab HS, Hyde JS, Feix JB. Aggregation state of spin-labeled cecropin AD in solution. Biochemistry. 1993 Nov 11/9/1993; 32(44): 11895-902. PMID: 7692965, ISSN: 0006-2960.

Mchaourab HS, Pfenninger S, Antholine WE, Felix CC, Hyde JS, Kroneck PM. Multiquantum EPR of the mixed valence copper site in nitrous oxide reductase. Biophys. J. 1993 May; 64(5): 1576-9. PMID: 8391869, PMCID: PMC1262484, PII: S0006-3495(93)81527-3, DOI: 10.1016/S0006-3495(93)81527-3, ISSN: 0006-3495.

Mchaourab HS, Christidis TC, and Hyde JS. Continuous wave multiquantum EPR spectroscopy. IV. Multiquantum electron-nuclear double resonance. J. Chem. Phys. 1993; 99: 4975.

Mchaourab HS, Pfenninger S, Antholine WE, Felix CC, Hyde JS, and Kroneck PMH. Multiquantum EPR of the copper mixed valence site in nitrous oxide reductase. Biophys. J. 1993; 64: 1576.

Mchaourab HS and Hyde JS. Dependence of the multiquantum EPR signal on the spin-lattice relaxation time. Effect of oxygen in spin-labeled membranes. J. Magn. Reson. 1993; 101B: 1748.

Mchaourab HS and Hyde JS. Continuous wave multiquantum EPR spectroscopy. III. Theory of intermodulation sidebands. J. Chem. Phys. 1993; 98: 1786.

Mchaourab HS, Christidis TC, Froncisz W, Sczaniecki PB, and Hyde JS. Multiple quantum electron-electron double resonance. J. Magn. Reson. 1991; 92: 420.

Available Postdoctoral Position Details
Posted: 8/20/2008
Postdoctoral position available in an interdisciplinary research program to investigate conformational changes during the functional cycles of multidrug transporters and/or the functional mechanism of small heat-shock proteins including lens á-crystallins. The experimental approach relies heavily on site-directed spin and fluorescence labeling and associated electron paramagnetic resonance and fluorescence spectroscopies. We are looking for a recent Ph.D. who is comfortable with these approaches and interested in learning new biophysical and biochemical techniques. Applicants should send a CV and 3 letters of recommendations to:
Hassane Mchaourab, Ph.D.
Department of Molecular Physiology and Biophysics
Vanderbilt University Medical Center
2215 Garland Avenue / 741 Light Hall
Nashville Tennessee 37232
Email:hassane.mchaourab@vanderbilt.edu