Faculty Appointments
Assistant Professor of Molecular Physiology & Biophysics
Education
Ph.D., Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TennesseeB.S., Chemistry, University of Alabama, Huntsville, Alabama
Office Address
746 Robinson Research Building, 2200 Pierce Avenue
Nashville, TN 37232
Nashville, TN 37232
Research Description
The Claxton laboratory employs tools of biochemistry and biophysics to explore the structure and function of membrane proteins that catalyze fundamental reactions in glucose and lipid metabolism. Disregulation or malfunction of these targets contributes to metabolic disorders such diabetes and glycogen storage disease. Our overall approach integrates knowledge of protein structure with sophisticated spectroscopic methods and reaction kinetics to develop mechanistic models of functional dynamics. The lab capitalizes on state-of-the-art instrumentation at Vanderbilt, including cryogenic electron microscopy (cryo-EM) and electron paramagnetic resonance (EPR), to facilitate discoveries. Our goal is to uncover relationships between target molecular properties and disease-linked variants to aid rational design of therapeutic strategies.
Research Keywords
Biochemistry, biophysics, structural biology, metabolism, diabetes
Publications
Overway EM, Bosma KJ, Claxton DP, Oeser JK, Singh K, Breidenbach LB, Mchaourab HS, Davis LK, O'Brien RM. Nonsynonymous single-nucleotide polymorphisms in the G6PC2 gene affect protein expression, enzyme activity, and fasting blood glucose. J Biol Chem [print-electronic]. 2022 Feb; 298(2): 101534. PMID: 34954144, PMCID: PMC8800118, PII: S0021-9258(21)01344-2, DOI: 10.1016/j.jbc.2021.101534, ISSN: 1083-351X.
Claxton DP, Overway EM, Oeser JK, O'Brien RM, Mchaourab HS. Biophysical and functional properties of purified glucose-6-phosphatase catalytic subunit 1. J Biol Chem [print-electronic]. 2022 Jan; 298(1): 101520. PMID: 34952005, PMCID: PMC8753184, PII: S0021-9258(21)01330-2, DOI: 10.1016/j.jbc.2021.101520, ISSN: 1083-351X.
Claxton DP, Jagessar KL, Mchaourab HS. Principles of Alternating Access in Multidrug and Toxin Extrusion (MATE) Transporters. J Mol Biol [print-electronic]. 2021 Aug 8/6/2021; 433(16): 166959. PMID: 33774036, PMCID: PMC8292195, PII: S0022-2836(21)00160-1, DOI: 10.1016/j.jmb.2021.166959, ISSN: 1089-8638.
Castellano S, Claxton DP, Ficici E, Kusakizako T, Stix R, Zhou W, Nureki O, Mchaourab HS, Faraldo-Gómez JD. Conserved binding site in the N-lobe of prokaryotic MATE transporters suggests a role for Na+ in ion-coupled drug efflux. J Biol Chem [print-electronic]. 2021 Jan 1/5/2021; PMID: 33402425, PII: RA120.016792, DOI: 10.1074/jbc.RA120.016792, ISSN: 1083-351X.
Han B, Porta JC, Hanks JL, Peskova Y, Binshtein E, Dryden K, Claxton DP, Mchaourab HS, Karakas E, Ohi MD, Kenworthy AK. Structure and assembly of CAV1 8S complexes revealed by single particle electron microscopy. Sci Adv [electronic-print]. 2020 Dec; 6(49): PMID: 33268374, PMCID: PMC7821874, PII: 6/49/eabc6185, DOI: 10.1126/sciadv.abc6185, ISSN: 2375-2548.
Jagessar KL, Claxton DP, Stein RA, Mchaourab HS. Sequence and structural determinants of ligand-dependent alternating access of a MATE transporter. Proc Natl Acad Sci U S A [print-electronic]. 2020 Mar 3/3/2020; 117(9): 4732-40. PMID: 32075917, PMCID: PMC7060674, PII: 1917139117, DOI: 10.1073/pnas.1917139117, ISSN: 1091-6490.
Jagessar KL, Mchaourab HS, Claxton DP. The N-terminal domain of an archaeal multidrug and toxin extrusion (MATE) transporter mediates proton coupling required for prokaryotic drug resistance. J Biol Chem [print-electronic]. 2019 Aug 8/23/2019; 294(34): 12807-14. PMID: 31289123, PMCID: PMC6709631, PII: S0021-9258(20)30312-4, DOI: 10.1074/jbc.RA119.009195, ISSN: 1083-351X.
Kusakizako T, Claxton DP, Tanaka Y, Maturana AD, Kuroda T, Ishitani R, Mchaourab HS, Nureki O. Structural Basis of H+-Dependent Conformational Change in a Bacterial MATE Transporter. Structure [print-electronic]. 2019 Feb 2/5/2019; 27(2): 293-301.e3-301.e3. PMID: 30449688, PMCID: PMC7935464, PII: S0969-2126(18)30365-4, DOI: 10.1016/j.str.2018.10.004, ISSN: 1878-4186.
Mishra S, Chandler SA, Williams D, Claxton DP, Koteiche HA, Stewart PL, Benesch JLP, Mchaourab HS. Engineering of a Polydisperse Small Heat-Shock Protein Reveals Conserved Motifs of Oligomer Plasticity. Structure [print-electronic]. 2018 Aug 8/7/2018; 26(8): 1116-1126.e4-1126.e4. PMID: 29983375, PMCID: PMC6563326, PII: S0969-2126(18)30179-5, DOI: 10.1016/j.str.2018.05.015, ISSN: 1878-4186.
Phulera S, Zhu H, Yu J, Claxton DP, Yoder N, Yoshioka C, Gouaux E. Cryo-EM structure of the benzodiazepine-sensitive a1ß1¿2S tri-heteromeric GABAA receptor in complex with GABA. Elife. 2018 Jul 7/25/2018; 7: PMID: 30044221, PMCID: PMC6086659, PII: 39383, DOI: 10.7554/eLife.39383, ISSN: 2050-084X.
Claxton DP, Jagessar KL, Steed PR, Stein RA, Mchaourab HS. Sodium and proton coupling in the conformational cycle of a MATE antiporter from Vibrio cholerae. Proc Natl Acad Sci U S A [print-electronic]. 2018 Jul 7/3/2018; 115(27): E6182-E6190-E6190. PMID: 29915043, PMCID: PMC6142240, PII: 1802417115, DOI: 10.1073/pnas.1802417115, ISSN: 1091-6490.
Paz A, Claxton DP, Kumar JP, Kazmier K, Bisignano P, Sharma S, Nolte SA, Liwag TM, Nayak V, Wright EM, Grabe M, Mchaourab HS, Abramson J. Conformational transitions of the sodium-dependent sugar transporter, vSGLT. Proc Natl Acad Sci U S A [print-electronic]. 2018 Mar 3/20/2018; 115(12): E2742-E2751-E2751. PMID: 29507231, PMCID: PMC5866573, PII: 1718451115, DOI: 10.1073/pnas.1718451115, ISSN: 1091-6490.
Claxton DP, Gouaux E. Expression and purification of a functional heteromeric GABAA receptor for structural studies. PLoS One. 2018; 13(7): e0201210. PMID: 30028870, PMCID: PMC6054424, PII: PONE-D-18-13357, DOI: 10.1371/journal.pone.0201210, ISSN: 1932-6203.
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]. 2017 Aug; 45: 100-8. PMID: 28040635, PMCID: PMC5491374, PII: S0959-440X(16)30171-3, DOI: 10.1016/j.sbi.2016.12.006, ISSN: 1879-033X.
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.
Claxton DP, Kazmier K, Mishra S, Mchaourab HS. Navigating Membrane Protein Structure, Dynamics, and Energy Landscapes Using Spin Labeling and EPR Spectroscopy. Methods 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.
Goehring A, Lee CH, Wang KH, Michel JC, Claxton DP, Baconguis I, Althoff T, Fischer S, Garcia KC, Gouaux E. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies. Nat Protoc [print-electronic]. 2014 Nov; 9(11): 2574-85. PMID: 25299155, PMCID: PMC4291175, PII: nprot.2014.173, DOI: 10.1038/nprot.2014.173, ISSN: 1750-2799.
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.
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.
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.
Gavira J JA, Claxton DP, Wang JH, Toh D, Meehan EJ, DiGiammarino EL. Purification, crystallization and preliminary X-ray analysis of Caenorhabditis elegans ubiquitin-conjugation enzyme M7.1. Acta Crystallogr D Biol Crystallogr [print-electronic]. 2003 Mar; 59(Pt 3): 544-6. PMID: 12595721, PII: S0907444903000039, DOI: 10.1107/s0907444903000039, ISSN: 0907-4449.
Claxton DP, Overway EM, Oeser JK, O'Brien RM, Mchaourab HS. Biophysical and functional properties of purified glucose-6-phosphatase catalytic subunit 1. J Biol Chem [print-electronic]. 2022 Jan; 298(1): 101520. PMID: 34952005, PMCID: PMC8753184, PII: S0021-9258(21)01330-2, DOI: 10.1016/j.jbc.2021.101520, ISSN: 1083-351X.
Claxton DP, Jagessar KL, Mchaourab HS. Principles of Alternating Access in Multidrug and Toxin Extrusion (MATE) Transporters. J Mol Biol [print-electronic]. 2021 Aug 8/6/2021; 433(16): 166959. PMID: 33774036, PMCID: PMC8292195, PII: S0022-2836(21)00160-1, DOI: 10.1016/j.jmb.2021.166959, ISSN: 1089-8638.
Castellano S, Claxton DP, Ficici E, Kusakizako T, Stix R, Zhou W, Nureki O, Mchaourab HS, Faraldo-Gómez JD. Conserved binding site in the N-lobe of prokaryotic MATE transporters suggests a role for Na+ in ion-coupled drug efflux. J Biol Chem [print-electronic]. 2021 Jan 1/5/2021; PMID: 33402425, PII: RA120.016792, DOI: 10.1074/jbc.RA120.016792, ISSN: 1083-351X.
Han B, Porta JC, Hanks JL, Peskova Y, Binshtein E, Dryden K, Claxton DP, Mchaourab HS, Karakas E, Ohi MD, Kenworthy AK. Structure and assembly of CAV1 8S complexes revealed by single particle electron microscopy. Sci Adv [electronic-print]. 2020 Dec; 6(49): PMID: 33268374, PMCID: PMC7821874, PII: 6/49/eabc6185, DOI: 10.1126/sciadv.abc6185, ISSN: 2375-2548.
Jagessar KL, Claxton DP, Stein RA, Mchaourab HS. Sequence and structural determinants of ligand-dependent alternating access of a MATE transporter. Proc Natl Acad Sci U S A [print-electronic]. 2020 Mar 3/3/2020; 117(9): 4732-40. PMID: 32075917, PMCID: PMC7060674, PII: 1917139117, DOI: 10.1073/pnas.1917139117, ISSN: 1091-6490.
Jagessar KL, Mchaourab HS, Claxton DP. The N-terminal domain of an archaeal multidrug and toxin extrusion (MATE) transporter mediates proton coupling required for prokaryotic drug resistance. J Biol Chem [print-electronic]. 2019 Aug 8/23/2019; 294(34): 12807-14. PMID: 31289123, PMCID: PMC6709631, PII: S0021-9258(20)30312-4, DOI: 10.1074/jbc.RA119.009195, ISSN: 1083-351X.
Kusakizako T, Claxton DP, Tanaka Y, Maturana AD, Kuroda T, Ishitani R, Mchaourab HS, Nureki O. Structural Basis of H+-Dependent Conformational Change in a Bacterial MATE Transporter. Structure [print-electronic]. 2019 Feb 2/5/2019; 27(2): 293-301.e3-301.e3. PMID: 30449688, PMCID: PMC7935464, PII: S0969-2126(18)30365-4, DOI: 10.1016/j.str.2018.10.004, ISSN: 1878-4186.
Mishra S, Chandler SA, Williams D, Claxton DP, Koteiche HA, Stewart PL, Benesch JLP, Mchaourab HS. Engineering of a Polydisperse Small Heat-Shock Protein Reveals Conserved Motifs of Oligomer Plasticity. Structure [print-electronic]. 2018 Aug 8/7/2018; 26(8): 1116-1126.e4-1126.e4. PMID: 29983375, PMCID: PMC6563326, PII: S0969-2126(18)30179-5, DOI: 10.1016/j.str.2018.05.015, ISSN: 1878-4186.
Phulera S, Zhu H, Yu J, Claxton DP, Yoder N, Yoshioka C, Gouaux E. Cryo-EM structure of the benzodiazepine-sensitive a1ß1¿2S tri-heteromeric GABAA receptor in complex with GABA. Elife. 2018 Jul 7/25/2018; 7: PMID: 30044221, PMCID: PMC6086659, PII: 39383, DOI: 10.7554/eLife.39383, ISSN: 2050-084X.
Claxton DP, Jagessar KL, Steed PR, Stein RA, Mchaourab HS. Sodium and proton coupling in the conformational cycle of a MATE antiporter from Vibrio cholerae. Proc Natl Acad Sci U S A [print-electronic]. 2018 Jul 7/3/2018; 115(27): E6182-E6190-E6190. PMID: 29915043, PMCID: PMC6142240, PII: 1802417115, DOI: 10.1073/pnas.1802417115, ISSN: 1091-6490.
Paz A, Claxton DP, Kumar JP, Kazmier K, Bisignano P, Sharma S, Nolte SA, Liwag TM, Nayak V, Wright EM, Grabe M, Mchaourab HS, Abramson J. Conformational transitions of the sodium-dependent sugar transporter, vSGLT. Proc Natl Acad Sci U S A [print-electronic]. 2018 Mar 3/20/2018; 115(12): E2742-E2751-E2751. PMID: 29507231, PMCID: PMC5866573, PII: 1718451115, DOI: 10.1073/pnas.1718451115, ISSN: 1091-6490.
Claxton DP, Gouaux E. Expression and purification of a functional heteromeric GABAA receptor for structural studies. PLoS One. 2018; 13(7): e0201210. PMID: 30028870, PMCID: PMC6054424, PII: PONE-D-18-13357, DOI: 10.1371/journal.pone.0201210, ISSN: 1932-6203.
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]. 2017 Aug; 45: 100-8. PMID: 28040635, PMCID: PMC5491374, PII: S0959-440X(16)30171-3, DOI: 10.1016/j.sbi.2016.12.006, ISSN: 1879-033X.
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.
Claxton DP, Kazmier K, Mishra S, Mchaourab HS. Navigating Membrane Protein Structure, Dynamics, and Energy Landscapes Using Spin Labeling and EPR Spectroscopy. Methods 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.
Goehring A, Lee CH, Wang KH, Michel JC, Claxton DP, Baconguis I, Althoff T, Fischer S, Garcia KC, Gouaux E. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies. Nat Protoc [print-electronic]. 2014 Nov; 9(11): 2574-85. PMID: 25299155, PMCID: PMC4291175, PII: nprot.2014.173, DOI: 10.1038/nprot.2014.173, ISSN: 1750-2799.
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.
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.
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.
Gavira J JA, Claxton DP, Wang JH, Toh D, Meehan EJ, DiGiammarino EL. Purification, crystallization and preliminary X-ray analysis of Caenorhabditis elegans ubiquitin-conjugation enzyme M7.1. Acta Crystallogr D Biol Crystallogr [print-electronic]. 2003 Mar; 59(Pt 3): 544-6. PMID: 12595721, PII: S0907444903000039, DOI: 10.1107/s0907444903000039, ISSN: 0907-4449.