Physiological and molecular triggers for SARS-CoV membrane fusion and entry into host cells.

Physiological and molecular triggers for SARS-CoV membrane fusion and entry into host cells.
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DOI:
10.1016/j.virol.2017.12.015
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发表时间:
2018-04
期刊:
影响因子:
3.7
通讯作者:
Whittaker GR
Whittaker GR
中科院分区:
医学3区
文献类型:
--
作者:
Millet JK;Whittaker GR

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在病毒进入过程中,包膜病毒需要其脂质包膜与宿主细胞膜融合。对于冠状病毒,这一关键步骤由病毒编码的刺突(S)蛋白控制,这是一种具有几个独特特征的I类病毒融合蛋白。冠状病毒进入是不寻常的,因为它通常是双相的,并且可以发生在细胞表面或附近或晚期内体中。冠状病毒S蛋白的结构、生物化学和分子生物学的最新进展揭示了冠状病毒进入的复杂性,特别是冠状病毒S介导的膜融合的分子触发因素。此外,冠状病毒融合肽(FP),融合蛋白的片段,插入到目标脂质双层膜融合过程中的表征,揭示了其特定的属性,赋予了一些不寻常的特性的S蛋白,如钙离子依赖性。这些不寻常的特征至少可以部分解释冠状病毒进入的双相性。本文以严重急性呼吸综合征冠状病毒(SARS-CoV)为模型病毒,综述了冠状病毒融合肽的研究进展,重点介绍了其在宿主细胞进入过程中的作用和特性。以SARS冠状病毒(SARS-CoV)为模型研究冠状病毒融合肽(FP)。基于功能和生物物理分析的证据表明,冠状病毒刺突蛋白S2′切割的下游区域是真正的FP,形成了扩展的“融合平台”。钙离子介导SARS冠状病毒膜融合的直接作用的证据。CoV FP的不寻常特征使其有别于其他I类融合肽。SARS-CoV细胞进入途径的双相性质可以用融合的钙依赖性来解释。
During viral entry, enveloped viruses require the fusion of their lipid envelope with host cell membranes. For coronaviruses, this critical step is governed by the virally-encoded spike (S) protein, a class I viral fusion protein that has several unique features. Coronavirus entry is unusual in that it is often biphasic in nature, and can occur at or near the cell surface or in late endosomes. Recent advances in structural, biochemical and molecular biology of the coronavirus S protein has shed light on the intricacies of coronavirus entry, in particular the molecular triggers of coronavirus S-mediated membrane fusion. Furthermore, characterization of the coronavirus fusion peptide (FP), the segment of the fusion protein that inserts to a target lipid bilayer during membrane fusion, has revealed its particular attributes which imparts some of the unusual properties of the S protein, such as Ca2+-dependency. These unusual characteristics can explain at least in part the biphasic nature of coronavirus entry. In this review, using severe acute respiratory syndrome coronavirus (SARS-CoV) as model virus, we give an overview of advances in research on the coronavirus fusion peptide with an emphasis on its role and properties within the biological context of host cell entry. SARS-CoV as model for studying the coronavirus (CoV) fusion peptide (FP). Evidence based on functional and biophysical analyses that reveal the region downstream of the coronavirus spike protein S2′ cleavage as the bona fide FP that forms an extended “fusion platform”. Evidence for a direct role for calcium cations in mediating membrane fusion of SARS-CoV. Unusual features of the CoV FP that set it apart from other class I fusion peptides. The biphasic nature of SARS-CoV cellular entry pathways can be explained by calcium-dependency of fusion.
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影响因子: --
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