Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: Structure and collective motions

被引:40
作者
Hung, A [1 ]
Tai, K [1 ]
Sansom, MSP [1 ]
机构
[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
基金
英国生物技术与生命科学研究理事会;
关键词
D O I
10.1529/biophysj.104.052878
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Multiple nanosecond duration molecular dynamics simulations were performed on the transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were free to move, whereas the outer ( M1, M3, M4) helix bundle was backbone restrained. The M2 helices largely retain their hydrogen-bonding pattern throughout the simulation, with some distortions in the helical end and loop regions. All of the M2 helices exhibit bending motions, with the hinge point in the vicinity of the central hydrophobic gate region ( corresponding to residues alpha L251 and alpha V255). The bending motions of the M2 helices lead to a degree of dynamic narrowing of the pore in the region of the proposed hydrophobic gate. Calculations of Born energy profiles for various structures along the simulation trajectory suggest that the conformations of the M2 bundle sampled correspond to a closed conformation of the channel. Principal components analyses of each of the M2 helices, and of the five-helix M2 bundle, reveal concerted motions that may be relevant to channel function. Normal mode analyses using the anisotropic network model reveal collective motions similar to those identified by principal components analyses.
引用
收藏
页码:3321 / 3333
页数:13
相关论文
共 77 条
  • [1] The nicotinic acetylcholine receptor: from molecular model to single-channel conductance
    Adcock, C
    Smith, GR
    Sansom, MSP
    [J]. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 2000, 29 (01): : 29 - 37
  • [2] Electrostatics and the ion selectivity of ligand-gated channels
    Adcock, C
    Smith, GR
    Sansom, MSP
    [J]. BIOPHYSICAL JOURNAL, 1998, 75 (03) : 1211 - 1222
  • [3] ESSENTIAL DYNAMICS OF PROTEINS
    AMADEI, A
    LINSSEN, ABM
    BERENDSEN, HJC
    [J]. PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1993, 17 (04): : 412 - 425
  • [4] AMIRI S, 2005, IN PRESS MOL MEMBR B
  • [5] Water dynamics and dewetting transitions in the small mechanosensitive channel MscS
    Anishkin, A
    Sukharev, S
    [J]. BIOPHYSICAL JOURNAL, 2004, 86 (05) : 2883 - 2895
  • [6] Anisotropy of fluctuation dynamics of proteins with an elastic network model
    Atilgan, AR
    Durell, SR
    Jernigan, RL
    Demirel, MC
    Keskin, O
    Bahar, I
    [J]. BIOPHYSICAL JOURNAL, 2001, 80 (01) : 505 - 515
  • [7] Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential
    Bahar, I
    Atilgan, AR
    Erman, B
    [J]. FOLDING & DESIGN, 1997, 2 (03): : 173 - 181
  • [8] Electrostatics of nanosystems: Application to microtubules and the ribosome
    Baker, NA
    Sept, D
    Joseph, S
    Holst, MJ
    McCammon, JA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) : 10037 - 10041
  • [9] HELIX GEOMETRY IN PROTEINS
    BARLOW, DJ
    THORNTON, JM
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1988, 201 (03) : 601 - 619
  • [10] Dynamite:: a simple way to gain insight into protein motions
    Barrett, CP
    Hall, BA
    Noble, MEM
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 : 2280 - 2287