The minimalist architectures of viroporins and their therapeutic implications.
The minimalist architectures of viroporins and their therapeutic implications.
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DOI：
10.1016/j.bbamem.2013.09.004
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发表时间：
2014-04
影响因子：
3.4
通讯作者：
Chou, James J.
中科院分区：
文献类型：
--
作者：
OuYang, Bo;Chou, James J.
许多病毒基因组编码小的完整膜蛋白，这些蛋白在膜中形成同源寡聚通道，并且它们跨膜屏障运输质子、阳离子和其他分子，以帮助病毒进入和成熟的各个步骤。这些病毒蛋白统称为病毒孔蛋白，对于病毒的致病性至关重要。在过去的五年中，通过核磁共振（NMR）、X射线晶体学和电子显微镜（EM）获得的结构表明，病毒孔蛋白通常采用简约的结构来实现其功能。已发现许多小分子可以干扰其通道活性，从而抑制病毒感染，使病毒孔蛋白成为治疗干预的潜在药物靶点。病毒孔蛋白的已知结构和抑制机制彼此显着不同，但它们之间有一些共同的原理。本文总结了病毒孔蛋白结构研究及其抗病毒化合物抑制作用的最新进展。本文是题为“病毒膜蛋白——细胞网络通道”特刊的一部分。概述病毒孔蛋白的已知结构 回顾流感 H + 通道和 HCV p7 通道采用的极简结构解决方案 讨论结构如何解释离子选择性和转运的分子机制 讨论金刚烷衍生物如何阻断 M2 和 p7 病毒孔蛋白以及耐药机制
Many viral genomes encode small, integral membrane proteins that form homo-oligomeric channels in membrane, and they transport protons, cations, and other molecules across the membrane barrier to aid various steps of viral entry and maturation. These viral proteins, collectively named viroporins, are crucial for viral pathogenicity. In the past five years, structures obtained by nuclear magnetic resonance (NMR), X-ray crystallography, and electron microscopy (EM) showed that viroporins often adopt minimalist architectures to achieve their functions. A number of small molecules have been identified to interfere with their channel activities and thereby inhibit viral infection, making viroporins potential drug targets for therapeutic intervention. The known architectures and inhibition mechanisms of viroporins differ significantly from each other, but some common principles are shared between them. This review article summarizes the recent developments in the structural investigation of viroporins and their inhibition by antiviral compounds. This article is part of a Special Issue entitled: Viral Membrane Proteins—Channels for Cellular Networking. Provide an overview of the known architectures of viroporins Review of the minimalist structural solutions adopted by influenza H + channels and HCV p7 channel Discuss how structures explain the molecular mechanism of ion selectivity and transport Discuss how adamantane derivatives block M2 and p7 viroporins and mechanism of drug resistance
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DOI：
10.1016/j.bbamem.2010.05.014
发表时间：
2011-03
期刊：
Biochimica et biophysica acta
影响因子：
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