A mechanism for acetylcholine receptor gating based on structure, coupling, phi, and flip

Journal of General Physiology

Volumn 149, Issue 1, 2016, Pages 85-103

  Gupta, Shaweta ^a   Chakraborty, Srirupa ^a   Vij, Ridhima ^a   Auerbach, Anthony ^a  

^a UNIVERSITY AT BUFFALO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NICOTINIC RECEPTOR;

ANIMAL; BINDING SITE; CHANNEL GATING; CONFORMATION; GENETICS; METABOLISM; MOLECULAR MODEL; MOUSE; MUTATION; PHYSIOLOGY; X RAY CRYSTALLOGRAPHY;

ANIMALS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; ION CHANNEL GATING; MICE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MUTATION; RECEPTORS, NICOTINIC;

EID: 85010223958     PISSN: 00221295     EISSN: 15407748     Source Type: Journal    
DOI: 10.1085/jgp.201611673     Document Type: Article

References (88)

1. Althoff, T., R.E. Hibbs, S. Banerjee, and E. Gouaux. 2014. X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors. Nature. 512:333-337. http://dx.doi.org/10.1038/nature13669
2. Auerbach, A. 2005. Gating of acetylcholine receptor channels: Brownian motion across a broad transition state. Proc. Natl. Acad. Sci. USA. 102:1408-1412. http://dx.doi.org/10.1073/pnas.0406787102
3. Auerbach, A. 2010. The gating isomerization of neuromuscular acetylcholine receptors. J. Physiol. 588:573-586. http://dx.doi.org/10.1113/jphysiol.2009.182774
4. Auerbach, A. 2012. Thinking in cycles: MWC is a good model for acetylcholine receptor-channels. J. Physiol. 590:93-98. http://dx.doi.org/10.1113/jphysiol.2011.214684
5. Bafna, P.A., P.G. Purohit, and A. Auerbach. 2008. Gating at the mouth of the acetylcholine receptor channel: energetic consequences of mutations in the alphaM2-cap. PLoS One. 3:e2515. http://dx.doi.org/10.1371/journal.pone.0002515
6. Bertozzi, C., I. Zimmermann, S. Engeler, R.J. Hilf, and R. Dutzler. 2016. Signal transduction at the domain interface of prokaryotic pentameric ligand-gated ion channels. PLoS Biol. 14:e1002393. (published erratum appears in PLoS Biol. 2016. 14:e1002390) http://dx.doi.org/10.1371/journal.pbio.1002393
7. Bolhuis, P.G., D. Chandler, C. Dellago, and P.L. Geissler. 2002. Transition path sampling: throwing ropes over rough mountain passes, in the dark. Annu. Rev. Phys. Chem. 53:291-318. http://dx.doi.org/10.1146/annurev.physchem.53.082301.113146
8. Bouzat, C. 2012. New insights into the structural bases of activation of Cys-loop receptors. J. Physiol. Paris. 106:23-33. http://dx.doi.org/10.1016/j.jphysparis.2011.09.012
9. Brooks, B.R., C.L. Brooks III, A.D. Mackerell Jr., L. Nilsson, R.J. Petrella, B. Roux, Y. Won, G. Archontis, C. Bartels, S. Boresch, et al. 2009. CHA RMM: the biomolecular simulation program. J. Comput. Chem. 30:1545-1614. http://dx.doi.org/10.1002/jcc.21287
10. Bu, Z., and D.J. Callaway. 2011. Proteins move! Protein dynamics and long-range allostery in cell signaling. Adv. Protein Chem. Struct. Biol. 83:163-221. http://dx.doi.org/10.1016/B978-0-12-381262-9.00005-7
11. Cadugan, D.J., and A. Auerbach. 2010. Linking the acetylcholine receptor-channel agonist-binding sites with the gate. Biophys. J. 99:798-807. http://dx.doi.org/10.1016/j.bpj.2010.05.008
12. Calimet, N., M. Simoes, J.P. Changeux, M. Karplus, A. Taly, and M. Cecchini. 2013. A gating mechanism of pentameric ligand-gated ion channels. Proc. Natl. Acad. Sci. USA. 110:E3987-E3996. http://dx.doi.org/10.1073/pnas.1313785110
13. Cecchini, M., and J.P. Changeux. 2015. The nicotinic acetylcholine receptor and its prokaryotic homologues: Structure, conformational transitions & allosteric modulation. Neuropharmacology. 96:137-149. http://dx.doi.org/10.1016/j.neuropharm.2014.12.006
14. Chakrapani, S., and A. Auerbach. 2005. A speed limit for conformational change of an allosteric membrane protein. Proc. Natl. Acad. Sci. USA. 102:87-92. http://dx.doi.org/10.1073/pnas.0406777102
15. Chakrapani, S., T.D. Bailey, and A. Auerbach. 2004. Gating dynamics of the acetylcholine receptor extracellular domain. J. Gen. Physiol. 123:341-356. http://dx.doi.org/10.1085/jgp.200309004
16. Changeux, J.P. 2014. Protein dynamics and the allosteric transitions of pentameric receptor channels. Biophys. Rev. 6:311-321. http://dx.doi.org/10.1007/s12551-014-0149-z
17. Cymes, G.D., and C. Grosman. 2012. The unanticipated complexity of the selectivity-filter glutamates of nicotinic receptors. Nat. Chem. Biol. 8:975-981. http://dx.doi.org/10.1038/nchembio.1092
18. Elenes, S., Y. Ni, G.D. Cymes, and C. Grosman. 2006. Desensitization contributes to the synaptic response of gain-of-function mutants of the muscle nicotinic receptor. J. Gen. Physiol. 128:615-627. http://dx.doi.org/10.1085/jgp.200609570
19. Garret, M., E. Boué-Grabot, and A. Taly. 2014. Long distance effect on ligand-gated ion channels extracellular domain may affect interactions with the intracellular machinery. Commun. Integr. Biol. 7:e27984. http://dx.doi.org/10.4161/cib.27984
20. Grosman, C., F.N. Salamone, S.M. Sine, and A. Auerbach. 2000a. The extracellular linker of muscle acetylcholine receptor channels is a gating control element. J. Gen. Physiol. 116:327-340. (published erratum appears in J. Gen. Physiol. 2000. 116:327) http://dx.doi.org/10.1085/jgp.116.3.327
21. Grosman, C., M. Zhou, and A. Auerbach. 2000b. Mapping the conformational wave of acetylcholine receptor channel gating. Nature. 403:773-776. http://dx.doi.org/10.1038/35001586
22. Gupta, S., P. Purohit, and A. Auerbach. 2013. Function of interfacial prolines at the transmitter-binding sites of the neuromuscular acetylcholine receptor. J. Biol. Chem. 288:12667-12679. http://dx.doi.org/10.1074/jbc. M112.443911
23. Harrington, W.F., H. Ueno, and J.S. Davis. 1988. Helix-coil melting in rigor and activated cross-bridges of skeletal muscle. Adv. Exp. Med. Biol. 226:307-318.
24. Hibbs, R.E., and E. Gouaux. 2011. Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature. 474:54-60. http://dx.doi.org/10.1038/nature10139
25. Humphrey, W., A. Dalke, and K. Schulten. 1996. VMD: visual molecular dynamics. J. Mol. Graph. 14:33-38. http://dx.doi.org/10.1016/0263-7855(96)00018-5
26. Jackson, M.B. 1984. Spontaneous openings of the acetylcholine receptor channel. Proc. Natl. Acad. Sci. USA. 81:3901-3904. http://dx.doi.org/10.1073/pnas.81.12.3901
27. Jackson, M.B. 1986. Kinetics of unliganded acetylcholine receptor channel gating. Biophys. J. 49:663-672. http://dx.doi.org/10.1016/S0006-3495(86)83693-1
28. Jackson, M.B. 1989. Perfection of a synaptic receptor: kinetics and energetics of the acetylcholine receptor. Proc. Natl. Acad. Sci. USA. 86:2199-2203. http://dx.doi.org/10.1073/pnas.86.7.2199
29. Jadey, S.V., P. Purohit, I. Bruhova, T.M. Gregg, and A. Auerbach. 2011. Design and control of acetylcholine receptor conformational change. Proc. Natl. Acad. Sci. USA. 108:4328-4333. http://dx.doi.org/10.1073/pnas.1016617108
30. Jadey, S., P. Purohit, and A. Auerbach. 2013. Action of nicotine and analogs on acetylcholine receptors having mutations of transmitter-binding site residue αG153. J. Gen. Physiol. 141:95-104. http://dx.doi.org/10.1085/jgp.201210896
31. Jaiteh, M., A. Taly, and J. Hénin. 2016. Evolution of pentameric ligand-gated ion channels: Pro-loop receptors. PLoS One. 11:e0151934. http://dx.doi.org/10.1371/journal.pone.0151934
32. Jha, A., and A. Auerbach. 2010. Acetylcholine receptor channels activated by a single agonist molecule. Biophys. J. 98:1840-1846. http://dx.doi.org/10.1016/j.bpj.2010.01.025
33. Jha, A., P. Purohit, and A. Auerbach. 2009. Energy and structure of the M2 helix in acetylcholine receptor-channel gating. Biophys. J. 96:4075-4084. http://dx.doi.org/10.1016/j.bpj.2009.02.030
34. Jha, A., S. Gupta, S.N. Zucker, and A. Auerbach. 2012. The energetic consequences of loop 9 gating motions in acetylcholine receptorchannels. J. Physiol. 590:119-129. http://dx.doi.org/10.1113/jphysiol.2011.213892
35. Jones, C.M., A. Ansari, E.R. Henry, G.W. Christoph, J. Hofrichter, and W.A. Eaton. 1992. Speed of intersubunit communication in proteins. Biochemistry. 31:6692-6702. http://dx.doi.org/10.1021/bi00144a008
36. Kabsch, W., and C. Sander. 1983. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 22:2577-2637. http://dx.doi.org/10.1002/bip.360221211
37. Karlin, A. 1967. On the application of "a plausible model" of allosteric proteins to the receptor for acetylcholine. J. Theor. Biol. 16:306-320. http://dx.doi.org/10.1016/0022-5193(67)90011-2
38. Kash, T.L., J.R. Trudell, and N.L. Harrison. 2004. Structural elements involved in activation of the γ-aminobutyric acid type A (GAB AA) receptor. Biochem. Soc. Trans. 32:540-546. http://dx.doi.org/10.1042/bst0320540
39. Kikkawa, M., E.P. Sablin, Y. Okada, H. Yajima, R.J. Fletterick, and N. Hirokawa. 2001. Switch-based mechanism of kinesin motors. Nature. 411:439-445. http://dx.doi.org/10.1038/35078000
40. Kjeldgaard, M., J. Nyborg, and B.F. Clark. 1996. The GTP binding motif: variations on a theme. FAS EB J. 10:1347-1368.
41. Lape, R., D. Colquhoun, and L.G. Sivilotti. 2008. On the nature of partial agonism in the nicotinic receptor superfamily. Nature. 454:722-727.
42. Lee, W.Y., and S.M. Sine. 2005. Principal pathway coupling agonist binding to channel gating in nicotinic receptors. Nature. 438:243-247. http://dx.doi.org/10.1038/nature04156
43. Lee, W.Y., C.R. Free, and S.M. Sine. 2008. Nicotinic receptor interloop proline anchors β1-β2 and Cys loops in coupling agonist binding to channel gating. J. Gen. Physiol. 132:265-278. http://dx.doi.org/10.1085/jgp.200810014
44. Lummis, S.C., D.L. Beene, L.W. Lee, H.A. Lester, R.W. Broadhurst, and D.A. Dougherty. 2005. Cis-trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel. Nature. 438:248-252. http://dx.doi.org/10.1038/nature04130
45. Ma, B., C.J. Tsai, T. Haliloglu, and R. Nussinov. 2011. Dynamic allostery: linkers are not merely flexible. Structure. 19:907-917. http://dx.doi.org/10.1016/j.str.2011.06.002
46. MacKerell, A.D., D. Bashford, M. Bellott, R.L. Dunbrack, J.D. Evanseck, M.J. Field, S. Fischer, J. Gao, H. Guo, S. Ha, et al. 1998. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B. 102:3586-3616. http://dx.doi.org/10.1021/jp973084f
47. Manjasetty, B.A., A.S. Halavaty, C.H. Luan, J. Osipiuk, R. Mulligan, K. Kwon, W.F. Anderson, and A. Joachimiak. 2016. Loop-to-helix transition in the structure of multidrug regulator AcrR at the entrance of the drug-binding cavity. J. Struct. Biol. 194:18-28. http://dx.doi.org/10.1016/j.jsb.2016.01.008
48. Miyazawa, A., Y. Fujiyoshi, M. Stowell, and N. Unwin. 1999. Nicotinic acetylcholine receptor at 4.6 Å resolution: transverse tunnels in the channel wall. J. Mol. Biol. 288:765-786. http://dx.doi.org/10.1006/jmbi.1999.2721
49. Miyazawa, A., Y. Fujiyoshi, and N. Unwin. 2003. Structure and gating mechanism of the acetylcholine receptor pore. Nature. 423:949-955. http://dx.doi.org/10.1038/nature01748
50. Monod, J., J. Wyman, and J.P. Changeux. 1965. On the nature of allosteric transitions: A plausible model. J. Mol. Biol. 12:88-118. http://dx.doi.org/10.1016/S0022-2836(65)80285-6
51. Morales-Perez, C.L., C.M. Noviello, and R.E. Hibbs. 2016. X-ray structure of the human α4β2 nicotinic receptor. Nature. 538:411-415. http://dx.doi.org/10.1038/nature19785
52. Mukhtasimova, N., C.J. daCosta, and S.M. Sine. 2016. Improved resolution of single channel dwell times reveals mechanisms of binding, priming, and gating in muscle AChR. J. Gen. Physiol. 148:43-63. http://dx.doi.org/10.1085/jgp.201611584
53. Nayak, T.K., and A. Auerbach. 2013. Asymmetric transmitter binding sites of fetal muscle acetylcholine receptors shape their synaptic response. Proc. Natl. Acad. Sci. USA. 110:13654-13659. http://dx.doi.org/10.1073/pnas.1308247110
54. Nayak, T.K., and A. Auerbach. 2015. Differences in agonist energy at the neurotransmitter binding sites in the neuromuscular acetylcholine receptors. Biophys. J. 108:429a-430a. http://dx.doi.org/10.1016/j.bpj.2014.11.2348
55. Nayak, T.K., I. Bruhova, S. Chakraborty, S. Gupta, W. Zheng, and A. Auerbach. 2014. Functional differences between neurotransmitter binding sites of muscle acetylcholine receptors. Proc. Natl. Acad. Sci. USA. 111:17660-17665. http://dx.doi.org/10.1073/pnas.1414378111
56. Nayak, T.K., S. Chakraborty, W. Zheng, and A. Auerbach. 2016. Structural correlates of affinity in fetal versus adult endplate nicotinic receptors. Nat. Commun. 7:11352. http://dx.doi.org/10.1038/ncomms11352
57. Nicolai, C., and F. Sachs. 2013. Solving ion channel kinetics with the QuB software. Biophys. Rev. Lett. 08:191-211. http://dx.doi.org/10.1142/S1793048013300053
58. Ohno, K., H.L. Wang, M. Milone, N. Bren, J.M. Brengman, S. Nakano, P. Quiram, J.N. Pruitt, S.M. Sine, and A.G. Engel. 1996. Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. Neuron. 17:157-170. http://dx.doi.org/10.1016/S0896-6273(00)80289-5
59. Oliveberg, M. 2001. Characterisation of the transition states for protein folding: towards a new level of mechanistic detail in protein engineering analysis. Curr. Opin. Struct. Biol. 11:94-100. http://dx.doi.org/10.1016/S0959-440X(00)00171-8
60. Popovych, N., S. Sun, R.H. Ebright, and C.G. Kalodimos. 2006. Dynamically driven protein allostery. Nat. Struct. Mol. Biol. 13:831-838. http://dx.doi.org/10.1038/nsmb1132
61. Prevost, M.S., L. Sauguet, H. Nury, C. Van Renterghem, C. Huon, F. Poitevin, M. Baaden, M. Delarue, and P.J. Corringer. 2012. A locally closed conformation of a bacterial pentameric protongated ion channel. Nat. Struct. Mol. Biol. 19:642-649. http://dx.doi.org/10.1038/nsmb.2307
62. Purohit, P., and A. Auerbach. 2009. Unliganded gating of acetylcholine receptor channels. Proc. Natl. Acad. Sci. USA. 106:115-120. http://dx.doi.org/10.1073/pnas.0809272106
63. Purohit, P., and A. Auerbach. 2010. Energetics of gating at the apoacetylcholine receptor transmitter binding site. J. Gen. Physiol. 135:321-331. http://dx.doi.org/10.1085/jgp.200910384
64. Purohit, P., and A. Auerbach. 2011. Glycine hinges with opposing actions at the acetylcholine receptor-channel transmitter binding site. Mol. Pharmacol. 79:351-359. http://dx.doi.org/10.1124/mol.110.068767
65. Purohit, P., and A. Auerbach. 2013. Loop C and the mechanism of acetylcholine receptor-channel gating. J. Gen. Physiol. 141:467-478. http://dx.doi.org/10.1085/jgp.201210946
66. Purohit, P., S. Gupta, S. Jadey, and A. Auerbach. 2013. Functional anatomy of an allosteric protein. Nat. Commun. 4:2984. http://dx.doi.org/10.1038/ncomms3984
67. Purohit, P., S. Chakraborty, and A. Auerbach. 2015. Function of the M1 p-helix in endplate receptor activation and desensitization. J. Physiol. 593:2851-2866. http://dx.doi.org/10.1113/JP270223
68. Roth, R., D. Gillespie, W. Nonner, and R.E. Eisenberg. 2008. Bubbles, gating, and anesthetics in ion channels. Biophys. J. 94:4282-4298. http://dx.doi.org/10.1529/biophysj.107.120493
69. Salamone, F.N., M. Zhou, and A. Auerbach. 1999. A re-examination of adult mouse nicotinic acetylcholine receptor channel activation kinetics. J. Physiol. 516:315-330. http://dx.doi.org/10.1111/j.1469-7793.1999.0315v.x
70. Sauguet, L., F. Poitevin, S. Murail, C. Van Renterghem, G. Moraga-Cid, L. Malherbe, A.W. Thompson, P. Koehl, P.J. Corringer, M. Baaden, and M. Delarue. 2013. Structural basis for ion permeation mechanism in pentameric ligand-gated ion channels. EMBO J. 32:728-741. http://dx.doi.org/10.1038/emboj.2013.17
71. Sauguet, L., A. Shahsavar, F. Poitevin, C. Huon, A. Menny, à. Nemecz, A. Haouz, J.P. Changeux, P.J. Corringer, and M. Delarue. 2014. Crystal structures of a pentameric ligand-gated ion channel provide a mechanism for activation. Proc. Natl. Acad. Sci. USA. 111:966-971. http://dx.doi.org/10.1073/pnas.1314997111
72. Sauguet, L., Z. Fourati, T. Prangé, M. Delarue, and N. Colloc'h. 2016. Structural basis for xenon inhibition in a cationic pentameric ligand-gated ion channel. PLoS One. 11:e0149795. http://dx.doi.org/10.1371/journal.pone.0149795
73. Sine, S.M. 2012. End-plate acetylcholine receptor: structure, mechanism, pharmacology, and disease. Physiol. Rev. 92:1189-1234. http://dx.doi.org/10.1152/physrev.00015.2011
74. Sine, S.M., K. Ohno, C. Bouzat, A. Auerbach, M. Milone, J.N. Pruitt, and A.G. Engel. 1995. Mutation of the acetylcholine receptor a subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity. Neuron. 15:229-239. http://dx.doi.org/10.1016/0896-6273(95)90080-2
75. Skolnick, J. 1987. Possible role of helix-coil transitions in the microscopic mechanism of muscle contraction. Biophys. J. 51:227-243. http://dx.doi.org/10.1016/S0006-3495(87)83328-3
76. Sorum, B., D. Czégé, and L. Csanády. 2015. Timing of CFTR pore opening and structure of its transition state. Cell. 163:724-733. http://dx.doi.org/10.1016/j.cell.2015.09.052
77. Sprang, S.R. 1997. G protein mechanisms: insights from structural analysis. Annu. Rev. Biochem. 66:639-678. http://dx.doi.org/10.1146/annurev.biochem.66.1.639
78. Taly, A., M. Delarue, T. Grutter, M. Nilges, N. Le Novère, P.J. Corringer, and J.P. Changeux. 2005. Normal mode analysis suggests a quaternary twist model for the nicotinic receptor gating mechanism. Biophys. J. 88:3954-3965. http://dx.doi.org/10.1529/biophysj.104.050229
79. Taly, A., J. Hénin, J.P. Changeux, and M. Cecchini. 2014. Allosteric regulation of pentameric ligand-gated ion channels: an emerging mechanistic perspective. Channels (Austin). 8:350-360. http://dx.doi.org/10.4161/chan.29444
80. Taylor, J.R. 1997. An Introduction to Error Analysis: The Study of Uncertainties in Physical Measurements. Second edition. University Science Books, New York. 327 pp.
81. Ternström, T., U. Mayor, M. Akke, and M. Oliveberg. 1999. From snapshot to movie: phi analysis of protein folding transition states taken one step further. Proc. Natl. Acad. Sci. USA. 96:14854-14859. http://dx.doi.org/10.1073/pnas.96.26.14854
82. Touw, W.G., C. Baakman, J. Black, T.A. te Beek, E. Krieger, R.P. Joosten, and G. Vriend. 2015. A series of PDB-related databanks for everyday needs. Nucleic Acids Res. 43:D364-D368. http://dx.doi.org/10.1093/nar/gku1028
83. Tsai, C.J., A. del Sol, and R. Nussinov. 2008. Allostery: absence of a change in shape does not imply that allostery is not at play. J. Mol. Biol. 378:1-11. http://dx.doi.org/10.1016/j.jmb.2008.02.034
84. Vij, R., P. Purohit, and A. Auerbach. 2015. Modal affinities of endplate acetylcholine receptors caused by loop C mutations. J. Gen. Physiol. 146:375-386. http://dx.doi.org/10.1085/jgp.201511503
85. Zheng, W., and D. Thirumalai. 2009. Coupling between normal modes drives protein conformational dynamics: illustrations using allosteric transitions in myosin II. Biophys. J. 96:2128-2137. http://dx.doi.org/10.1016/j.bpj.2008.12.3897
86. Zhou, Y., J.E. Pearson, and A. Auerbach. 2005. Phi-value analysis of a linear, sequential reaction mechanism: theory and application to ion channel gating. Biophys. J. 89:3680-3685. http://dx.doi.org/10.1529/biophysj.105.067215
87. Zhu, F., and G. Hummer. 2010. Pore opening and closing of a pentameric ligand-gated ion channel. Proc. Natl. Acad. Sci. USA. 107:19814-19819. http://dx.doi.org/10.1073/pnas.1009313107
88. Zhu, F., and G. Hummer. 2012. Theory and simulation of ion conduction in the pentameric GLIC channel. J. Chem. Theory Comput. 8:3759-3768. http://dx.doi.org/10.1021/ct2009279