Concerted deletions eliminate a neutralizing supersite in SARS-CoV-2 BA.2.87.1 spike

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2024-08-21 DOI:10.1016/j.str.2024.07.020

Helen M.E. Duyvesteyn, Aiste Dijokaite-Guraliuc, Chang Liu, Piyada Supasa, Barbara Kronsteiner, Katie Jeffery, Lizzie Stafford, Paul Klenerman, Susanna J. Dunachie, Juthathip Mongkolsapaya, Elizabeth E. Fry, Jingshan Ren, David I. Stuart, Gavin R. Screaton

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Abstract

BA.2.87.1 represents a major shift in the BA.2 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is unusual in having two lengthy deletions of polypeptide in the spike (S) protein, one of which removes a beta-strand. Here we investigate its neutralization by a variety of sera from infected and vaccinated individuals and determine its spike (S) ectodomain structure. The BA.2.87.1 receptor binding domain (RBD) is structurally conserved and the RBDs are tightly packed in an “all-down” conformation with a small rotation relative to the trimer axis as compared to the closest previously observed conformation. The N-terminal domain (NTD) maintains a remarkably similar structure overall; however, the rearrangements resulting from the deletions essentially destroy the so-called supersite epitope and eliminate one glycan site, while a mutation creates an additional glycan site, effectively shielding another NTD epitope. BA.2.87.1 is relatively easily neutralized but acquisition of additional mutations in the RBD could increase antibody escape allowing it to become a dominant sub-lineage.

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协同删除消除了 SARS-CoV-2 BA.2.87.1 穗状病毒中的中和超位点

BA.2.87.1 代表了严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）BA.2 系的一个重大转变，其不同寻常之处在于尖峰（S）蛋白中有两个长的多肽缺失，其中一个缺失去除了一个 beta 链。在此，我们研究了来自感染者和疫苗接种者的多种血清对它的中和作用，并确定了它的尖峰（S）外域结构。BA.2.87.1 受体结合结构域（RBD）在结构上是保守的，RBD 紧密排列成 "全向下 "构象，与之前观察到的最接近的构象相比，相对于三聚体轴的旋转很小。N 端结构域（NTD）在整体上保持了极为相似的结构；然而，缺失导致的重排基本上破坏了所谓的超位表位，并消除了一个聚糖位点，而突变则产生了一个额外的聚糖位点，有效地屏蔽了另一个 NTD 表位。BA.2.87.1 比较容易被中和，但在 RBD 中获得额外的突变可能会增加抗体逃逸，使其成为一个优势亚系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.