Crystal structure of the post-fusion core of the Human coronavirus 229E spike protein at 1.86 Å resolution.
Crystal structure of the post-fusion core of the Human coronavirus 229E spike protein at 1.86 Å resolution.
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人类冠状病毒 229E 刺突蛋白融合后核心的晶体结构，分辨率为 1.86 A。
DOI：
10.1107/s2059798318008318
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发表时间：
2018-09-01
期刊：
影响因子：
--
通讯作者：
Yang B
中科院分区：
文献类型：
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作者：
Yan L;Meng B;Xiang J;Wilson IA;Yang B
人类冠状病毒229E （HCoV‐229E）通常在健康成人中引起轻度上呼吸道感染，但在免疫系统较弱的个体中可能导致严重并发症或死亡。HCoV‐229E的病毒进入是由其刺突(S)蛋白介导的，其中S1结构域促进与宿主细胞的附着，S2结构域参与随后的病毒与宿主膜的融合。在融合过程中，S2结构域的两个七重体HR1和HR2组装成一个六螺旋膜融合结构，称为融合核。在这里，以1.86 Å分辨率确定了HCoV - 229E的完整融合核结构，代表了迄今为止已发表的人类甲型冠状病毒（α - HCoV）融合核结构中最完整的融合后构像。HCoV‐229E融合核的整体结构与SARS、MERS和HCoV‐NL63相似，但其3HR1核的包装与SARS和MERS不同，它包含更多的非规范“x”和“da”层。并排静电表面比较表明，α - HCoV和β - HCoV的静电表面电位在某些位置相反，并且HCoV - 229E表面似乎是各种HCoV中最疏水的。除了HR1和HR2之间高度保守的疏水相互作用外，一些极性和静电相互作用在不同的hcov之间也得到了很好的保存。本研究增加了hcov的结构分析，有助于基于结构的泛冠状病毒小分子或肽的设计，以抑制病毒融合。以1.86 Å分辨率测定了人冠状病毒229E刺突蛋白的完整融合后核心结构。比较不同人类冠状病毒中七肽重复HR1和HR2之间的相互作用揭示了一些差异，在设计针对HR1的泛冠状病毒HR2模拟抑制剂时应考虑到这些差异。
Human coronavirus 229E (HCoV‐229E) usually causes mild upper respiratory infections in heathy adults, but may lead to severe complications or mortality in individuals with weakened immune systems. Virus entry of HCoV‐229E is mediated by its spike (S) protein, where the S1 domain facilitates attachment to host cells and the S2 domain is involved in subsequent fusion of the virus and host membranes. During the fusion process, two heptad repeats, HR1 and HR2, in the S2 domain assemble into a six‐helix membrane‐fusion structure termed the fusion core. Here, the complete fusion‐core structure of HCoV‐229E has been determined at 1.86 Å resolution, representing the most complete post‐fusion conformation thus far among published human alphacoronavirus (α‐HCoV) fusion‐core structures. The overall structure of the HCoV‐229E fusion core is similar to those of SARS, MERS and HCoV‐NL63, but the packing of its 3HR1 core differs from those of SARS and MERS in that it contains more noncanonical `x' and `da' layers. Side‐by‐side electrostatic surface comparisons reveal that the electrostatic surface potentials are opposite in α‐HCoVs and β‐HCoVs at certain positions and that the HCoV‐229E surface also appears to be the most hydrophobic among the various HCoVs. In addition to the highly conserved hydrophobic interactions between HR1 and HR2, some polar and electrostatic interactions are also well preserved across different HCoVs. This study adds to the structural profiling of HCoVs to aid in the structure‐based design of pan‐coronavirus small molecules or peptides to inhibit viral fusion. The complete post‐fusion core structure of the Human coronavirus 229E spike protein was determined at 1.86 Å resolution. Comparison of the interactions between heptad repeats HR1 and HR2 in different human coronaviruses reveals some differences, which should be taken into consideration when designing pan‐coronavirus HR2‐mimicking inhibitors that target HR1.