Genotype-specific differences in structural features of hepatitis C virus (HCV) p7 membrane protein.
Genotype-specific differences in structural features of hepatitis C virus (HCV) p7 membrane protein.
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基因型特异性丙型肝炎病毒（HCV）P7膜蛋白的特异性差异。
DOI：
10.1016/j.bbamem.2015.03.006
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Fischer WB
中科院分区：
文献类型：
--
作者：
Kalita MM;Griffin S;Chou JJ;Fischer WB
由丙型肝炎病毒（HCV）编码的63个氨基酸的多位膜蛋白p7参与受感染细胞内跨膜的电化学梯度的调节。与来自多个基因型的p7相关的结构信息已经在计算机中产生（例如基因型（GT）1a），以及从单体和六聚体结构形式的实验中获得（分别为GT 1b和5a）。然而，序列多样性和结构差异意味着它们的信道选通行为的比较迄今尚未被模拟。这里，优化单体GT 1a蛋白的分子模型并组装成六聚体束，用于与5a六聚体结构和使用GT 1b单体结构产生的另一个六聚体束进行比较。在水合脂质双层中的分子动力学（MD）模拟（Gromos 96（ffG 45 a3））期间，以及在“低pH”下模拟时，所有束倾向于变成紧凑结构，根据一些功能研究，这可能触发通道开放。GT 1a和1b通道模型都是通过平行排列的螺旋的运动来门控的，但GT 5a蛋白的情况更复杂，涉及短的N-末端螺旋。然而，所有的束显示通过监测孔隙内的水动力学确定的脉动动力学。HCV p7六聚体束的基因型特异性结构特征基因型1a束的计算机构建模型与来自NMR的基因型1b和5a的模型进行比较基因型1a和1b通道通过平行排列的螺旋的移动门控。基因型5a束模型的复杂场景所有束显示脉动动力学。
The 63 amino acid polytopic membrane protein, p7, encoded by hepatitis C virus (HCV) is involved in the modulation of electrochemical gradients across membranes within infected cells. Structural information relating to p7 from multiple genotypes has been generated in silico (e.g. genotype (GT) 1a), as well as obtained from experiments in form of monomeric and hexameric structures (GTs 1b and 5a, respectively). However, sequence diversity and structural differences mean that comparison of their channel gating behaviour has not thus far been simulated. Here, a molecular model of the monomeric GT 1a protein is optimized and assembled into a hexameric bundle for comparison with both the 5a hexamer structure and another hexameric bundle generated using the GT 1b monomer structure. All bundles tend to turn into a compact structure during molecular dynamics (MD) simulations (Gromos96 (ffG45a3)) in hydrated lipid bilayers, as well as when simulated at ‘low pH’, which may trigger channel opening according to some functional studies. Both GT 1a and 1b channel models are gated via movement of the parallel aligned helices, yet the scenario for the GT 5a protein is more complex, with a short N-terminal helix being involved. However, all bundles display pulsatile dynamics identified by monitoring water dynamics within the pore. Genotype specific structural features of hexameric bundles of p7 of HCV In silico built models of genotype 1a bundle compared with models of genotypes 1b and 5a from NMR Genotype 1a and 1b channels are gated via movement of the parallel aligned helices. Complex scenario for genotype 5a bundle model All bundles show pulsatile dynamics.
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影响因子：
3.5
作者：
Grice, AL;Kerr, ID;Sansom, MSP
通讯作者：
Sansom, MSP
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG
DOI：
10.1016/b978-0-12-394305-7.00006-9
发表时间：
2012
影响因子：
--
作者：
Fischer WB;Wang YT;Schindler C;Chen CP
通讯作者：
Chen CP
影响因子：
2.9
作者：
Cordes, FS;Tustian, AD;Fischer, WB
通讯作者：
Fischer, WB
影响因子：
2.2
作者：
Hsu HJ;Fischer WB
通讯作者：
Fischer WB