Pores Formed by the Nicotinic Receptor M2delta Peptide: a Molecular Dynamics Simulation Study

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2003 Jan 14

PMID 12524262

Citations 15

Authors

R J Law

D P Tieleman

M S P Sansom

Affiliations

Soon will be listed here.

Abstract

The M2delta peptide self-assembles to form a pentameric bundle of transmembrane alpha-helices that is a model of the pore-lining region of the nicotinic acetylcholine receptor. Long (>15 ns) molecular dynamics simulations of a model of the M2delta(5) bundle in a POPC bilayer have been used to explore the conformational dynamics of the channel assembly. On the timescale of the simulation, the bundle remains relatively stable, with the polar pore-lining side chains remaining exposed to the lumen of the channel. Fluctuations at the helix termini, and in the helix curvature, result in closing/opening transitions at both mouths of the channel, on a timescale of approximately 10 ns. On average, water within the pore lumen diffuses approximately 4x more slowly than water outside the channel. Examination of pore water trajectories reveals both single-file and path-crossing regimes to occur at different times within the simulation.

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References

Smart O, Goodfellow J, Wallace B . The pore dimensions of gramicidin A. Biophys J. 1993; 65(6):2455-60. PMC: 1225986. DOI: 10.1016/S0006-3495(93)81293-1. View

Sansom M . Structure and function of channel-forming peptaibols. Q Rev Biophys. 1993; 26(4):365-421. DOI: 10.1017/s0033583500002833. View

Berger O, Edholm O, Jahnig F . Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J. 1997; 72(5):2002-13. PMC: 1184396. DOI: 10.1016/S0006-3495(97)78845-3. View

Smart O, Neduvelil J, Wang X, Wallace B, Sansom M . HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J Mol Graph. 1996; 14(6):354-60, 376. DOI: 10.1016/s0263-7855(97)00009-x. View

Bowie J . Helix packing in membrane proteins. J Mol Biol. 1997; 272(5):780-9. DOI: 10.1006/jmbi.1997.1279. View

Sansom M, Smith G, Adcock C, Biggin P . The dielectric properties of water within model transbilayer pores. Biophys J. 1997; 73(5):2404-15. PMC: 1181142. DOI: 10.1016/S0006-3495(97)78269-9. View

Kovacs F, Cross T . Transmembrane four-helix bundle of influenza A M2 protein channel: structural implications from helix tilt and orientation. Biophys J. 1997; 73(5):2511-7. PMC: 1181152. DOI: 10.1016/S0006-3495(97)78279-1. View

Roux B . Influence of the membrane potential on the free energy of an intrinsic protein. Biophys J. 1997; 73(6):2980-9. PMC: 1181204. DOI: 10.1016/S0006-3495(97)78327-9. View

Zhong Q, Jiang Q, Moore P, Newns D, Klein M . Molecular dynamics simulation of a synthetic ion channel. Biophys J. 1998; 74(1):3-10. PMC: 1299356. DOI: 10.1016/S0006-3495(98)77761-6. View

10.

Zhong Q, Moore P, Newns D, Klein M . Molecular dynamics study of the LS3 voltage-gated ion channel. FEBS Lett. 1998; 427(2):267-70. DOI: 10.1016/s0014-5793(98)00304-4. View

11.

Perozo E, Cortes D, Cuello L . Three-dimensional architecture and gating mechanism of a K+ channel studied by EPR spectroscopy. Nat Struct Biol. 1998; 5(6):459-69. DOI: 10.1038/nsb0698-459. View

12.

Adcock C, Smith G, Sansom M . Electrostatics and the ion selectivity of ligand-gated channels. Biophys J. 1998; 75(3):1211-22. PMC: 1299796. DOI: 10.1016/S0006-3495(98)74040-8. View

13.

Marassi F, Opella S . NMR structural studies of membrane proteins. Curr Opin Struct Biol. 1998; 8(5):640-8. PMC: 3282058. DOI: 10.1016/s0959-440x(98)80157-7. View

14.

Chang G, Spencer R, Lee A, Barclay M, Rees D . Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. Science. 1998; 282(5397):2220-6. DOI: 10.1126/science.282.5397.2220. View

15.

Shen Y, Kong Y, Ma J . Intrinsic flexibility and gating mechanism of the potassium channel KcsA. Proc Natl Acad Sci U S A. 2002; 99(4):1949-53. PMC: 122300. DOI: 10.1073/pnas.042650399. View

16.

Panicker S, Cruz H, Arrabit C, Slesinger P . Evidence for a centrally located gate in the pore of a serotonin-gated ion channel. J Neurosci. 2002; 22(5):1629-39. PMC: 6758895. View

17.

Tajkhorshid E, Nollert P, Jensen M, Miercke L, OConnell J, Stroud R . Control of the selectivity of the aquaporin water channel family by global orientational tuning. Science. 2002; 296(5567):525-30. DOI: 10.1126/science.1067778. View

18.

Reeves D, Lummis S . The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand-gated ion channel (review). Mol Membr Biol. 2002; 19(1):11-26. DOI: 10.1080/09687680110110048. View

19.

Shrivastava I, Sansom M . Molecular dynamics simulations and KcsA channel gating. Eur Biophys J. 2002; 31(3):207-16. DOI: 10.1007/s00249-002-0209-3. View

20.

Jiang Y, Lee A, Chen J, Cadene M, Chait B, MacKinnon R . Crystal structure and mechanism of a calcium-gated potassium channel. Nature. 2002; 417(6888):515-22. DOI: 10.1038/417515a. View