小柯机器人

科学家报道新冠病毒蛋白与受体ACE2结合结构
2020-03-31 15:57

2020年3月30日,《自然》杂志在线发表了清华大学王新泉和张林琦等研究人员的合作成果。他们的最新研究揭示了新冠病毒(SARS-CoV-2)突刺受体结合域与ACE2受体结合的结构。

为了更好地了解在原子水平上感染的初始步骤,研究人员报道了2.45Å分辨率下与细胞受体ACE2结合的SARS-CoV-2突刺受体结合域(RBD)的晶体结构。SARS-CoV-2 RBD的总体ACE2结合模式几乎与SARS-CoV RBD的相同,后者也利用ACE2作为细胞受体。
 
结构分析确定了SARS-CoV-2 RBD中对ACE2结合至关重要的残基,其中大多数是高度保守的或者与SARS-CoV RBD中的残基具有相似的侧链特性。这种结构和序列上的相似性表明了SARS-CoV-2和SARS-CoV RBD之间的趋同进化,从而增强了与ACE2的结合,尽管SARS-CoV-2不会与SARS和与SARS相关的冠状病毒在进化树上高度近似。
 
研究人员还使用SARS-CoV-2 RBD分析了靶向RBD的两种SARS-CoV抗体表位,从而为深入鉴定交叉反应性抗体提供了见解。
 
附:英文原文

Title: Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Author: Jun Lan, Jiwan Ge, Jinfang Yu, Sisi Shan, Huan Zhou, Shilong Fan, Qi Zhang, Xuanling Shi, Qisheng Wang, Linqi Zhang, Xinquan Wang

Issue&Volume: 2020-03-30

Abstract: To better understand the initial step of infection at an atomic level, we determined the crystal structure of the SARS-CoV-2 spike receptor-binding domain (RBD) bound to the cell receptor ACE2 at 2.45 resolution. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are critical for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly argue for convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1–3,5. The epitopes of two SARS-CoV antibodies targeting the RBD are also analysed with the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.

DOI: 10.1038/s41586-020-2180-5

Source: https://www.nature.com/articles/s41586-020-2180-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0