A prokaryotic glutamate receptor: homology modelling and molecular dynamics simulations of GluR0

被引:18
作者
Arinaminpathy, Y [1 ]
Biggin, PC [1 ]
Shrivastava, IH [1 ]
Sansom, MSP [1 ]
机构
[1] Univ Oxford, Dept Biochem, Mol Biophys Lab, Oxford OX1 3QU, England
基金
英国惠康基金; 英国医学研究理事会; 英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
ion channel; receptor; molecular model; MD simulation; membrane protein;
D O I
10.1016/S0014-5793(03)01036-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
GluR0 is a prokaryotic homologue of mammalian glutamate receptors that forms glutamate-activated, potassium-selective ion channels. The topology of its transmembrane (TM) domain is similar to that of simple potassium channels such as KcsA. Two plausible alignments of the sequence of the TM domain of GluR0 with KcsA are possible, differing in the region of the P helix. We have constructed homology models based on both alignments and evaluated them using 6 ns duration molecular dynamics simulations in a membrane-mimetic environment. One model, in which an insertion in GluR0 relative to KcsA is located in the loop between the M1 and P helices, is preferred on the basis of lower structural drift and maintenance of the P helix conformation during simulation. This model also exhibits inter-subunit salt bridges that help to stabilise the TM domain tetramer. During the simulation, concerted K+ ion-water movement along the selectivity filter is observed, as is the case in simulations of KcsA. K+ ion exit from the central cavity is associated with opening of the hydrophobic gate formed by the C-termini of the M2 helices. In the intact receptor the opening of this gate will be controlled by interactions with the extramembranous ligand-binding domains. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
引用
收藏
页码:321 / 327
页数:7
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