Sansom M S, Forrest L R, Bull R
Department of Biochemistry, University of Oxford, UK.
Bioessays. 1998 Dec;20(12):992-1000. doi: 10.1002/(SICI)1521-1878(199812)20:12<992::AID-BIES5>3.0.CO;2-7.
In a number of membrane-bound viruses, ion channels are formed by integral membrane proteins. These channel proteins include M2 from influenza A, NB from influenza B, and, possibly, Vpu from HIV-1. M2 is important in facilitating uncoating of the influenza A viral genome and is the target of amantadine, an anti-influenza drug. The biological roles of NB and Vpu are less certain. In all cases, the protein contains a single transmembrane alpha-helix close to its N-terminus. Channels can be formed by homo-oligomerization of these proteins, yielding bundles of transmembrane helices that span the membrane and surround a central ion-permeable pore. Molecular modeling may be used to integrate and interpret available experimental data concerning the structure of such transmembrane pores. This has proved successful for the M2 channel domain, where two independently derived models are in agreement with one another, and with solid-state nuclear magnetic resonance (NMR) data. Simulations based on channel models may yield insights into possible ion conduction and selectivity mechanisms.
在许多膜结合病毒中，离子通道由整合膜蛋白形成。这些通道蛋白包括甲型流感病毒的M2、乙型流感病毒的NB以及可能的HIV-1的Vpu。M2在促进甲型流感病毒基因组脱壳过程中起重要作用，并且是抗流感药物金刚烷胺的作用靶点。NB和Vpu的生物学作用尚不太明确。在所有情况下，该蛋白在其N端附近都含有一个单一的跨膜α螺旋。这些蛋白通过同型寡聚化可形成通道，产生跨膜螺旋束，这些螺旋束跨越膜并围绕一个中央离子通透孔。分子建模可用于整合和解释有关此类跨膜孔结构的现有实验数据。这已在M2通道结构域中证明是成功的，在该结构域中，两个独立推导的模型相互一致，并且与固态核磁共振（NMR）数据一致。基于通道模型的模拟可能会深入了解可能的离子传导和选择性机制。
