The Viral Class II Membrane Fusion Machinery: Divergent Evolution from an Ancestral Heterodimer.
The Viral Class II Membrane Fusion Machinery: Divergent Evolution from an Ancestral Heterodimer.
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病毒II类膜融合机械：与祖先异二聚体不同的进化。
DOI：
10.3390/v13122368
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发表时间：
2021-11-26
期刊：
影响因子：
--
通讯作者：
Rey FA
中科院分区：
文献类型：
--
作者：
Guardado-Calvo P;Rey FA
包膜病毒进入细胞的一个关键步骤是病毒和细胞脂双层的合并。这一过程是由存在于病毒粒子表面的专用膜融合蛋白(MFP)驱动的，该蛋白经历了由与靶细胞相互作用引发的膜融合构象变化。病毒MFP在结构上得到了广泛的研究，根据其三维折叠的不同分为三类。因为同一类的MFP在其他无关的病毒中被发现，它们在类内的结构同源性表明水平的基因交换。我们把重点放在II类融合机制上，它由两个以异二聚体形式结合的糖蛋白组成。它们在感染细胞的内质网中折叠在一起，使MFP采用一种构象，只有在与靶细胞接触时才能对特定线索做出反应，从而避免在生产细胞中过早融合。我们发现，尽管在进化过程中II类伴随蛋白(AP)在3D折叠中的分歧比实际的MFP要大得多，但它也来自一个遥远的共同祖先，表现出一个不变的核心，分别由β带状结构域和C末端免疫球蛋白样结构域扮演不同的功能角色--与MFP的异型相互作用，以及同型AP/AP接触形成尖峰。我们的分析表明，用现代结构预测算法很容易识别II类AP，为疫苗设计提供了有用的信息。
A key step during the entry of enveloped viruses into cells is the merger of viral and cell lipid bilayers. This process is driven by a dedicated membrane fusion protein (MFP) present at the virion surface, which undergoes a membrane–fusogenic conformational change triggered by interactions with the target cell. Viral MFPs have been extensively studied structurally, and are divided into three classes depending on their three-dimensional fold. Because MFPs of the same class are found in otherwise unrelated viruses, their intra-class structural homology indicates horizontal gene exchange. We focus this review on the class II fusion machinery, which is composed of two glycoproteins that associate as heterodimers. They fold together in the ER of infected cells such that the MFP adopts a conformation primed to react to specific clues only upon contact with a target cell, avoiding premature fusion in the producer cell. We show that, despite having diverged in their 3D fold during evolution much more than the actual MFP, the class II accompanying proteins (AP) also derive from a distant common ancestor, displaying an invariant core formed by a β-ribbon and a C-terminal immunoglobulin-like domain playing different functional roles—heterotypic interactions with the MFP, and homotypic AP/AP contacts to form spikes, respectively. Our analysis shows that class II APs are easily identifiable with modern structural prediction algorithms, providing useful information in devising immunogens for vaccine design.
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DOI：
10.3390/v6041801
发表时间：
2014-04-21
期刊：
Viruses
影响因子：
--
作者：
Cifuentes-Muñoz N;Salazar-Quiroz N;Tischler ND
通讯作者：
Tischler ND
影响因子：
64.8
作者：
Basore K;Ma H;Kafai NM;Mackin S;Kim AS;Nelson CA;Diamond MS;Fremont DH
通讯作者：
Fremont DH
影响因子：
7.7
作者：
Feng, Juan;Dong, Xianchi;Springer, Timothy A.
通讯作者：
Springer, Timothy A.
影响因子：
5.7
作者：
Baquero, Eduard;Fedry, Juliette;Rey, Felix A.
通讯作者：
Rey, Felix A.
重新审视一个老朋友：α病毒结构和组装中的新发现。
影响因子：
5.9
作者：
Button JM;Qazi SA;Wang JC;Mukhopadhyay S
通讯作者：
Mukhopadhyay S