小柯机器人

以色列魏茨曼科学研究所Ron Diskin小组揭示拉沙病毒刺突复合体的结构和受体识别机制。相关论文于2022年2月16日在线发表在《自然》杂志上。

研究人员表示，拉沙病毒（LASV）是一种人类病原体，引起大量的发病和死亡。与其他沙粒病毒科相似，它的表面有一个I类突刺状复合物，便于进入细胞。该病毒的细胞受体是matriglycan，一种存在于α-dystroglycan上的线性碳水化合物，但LASV用来识别这种糖的分子机制尚不清楚。此外，LASV和其他沙粒病毒有一个独特的信号肽，形成了成熟突刺的一个整体和功能上的重要部分；但信号肽在膜上的结构、功能和拓扑结构仍不确定。

研究人员了一个完整的LASV突刺复合物结构，发现信号肽穿过膜一次，其氨基端位于细胞外区域。与双面结构域切换机制一起，信号肽有助于将突刺复合物稳定在其原始构象中。这个结构揭示了LASV突刺复合物预装了matriglycan，表明了α-dystroglycan嗜性的沙粒病毒受体识别的结合机制和合理性。这一发现使研究人员进一步了解了病毒排出的机制，并可能促进利用这一结合位点的新型疗法设计。

附：英文原文

Title: Structure and receptor recognition by the Lassa virus spike complex

Author: Katz, Michael, Weinstein, Jonathan, Eilon-Ashkenazy, Maayan, Gehring, Katrin, Cohen-Dvashi, Hadas, Elad, Nadav, Fleishman, Sarel J., Diskin, Ron

Issue&Volume: 2022-02-16

Abstract: Lassa virus (LASV) is a human pathogen, causing substantial morbidity and mortality1,2. Similar to other Arenaviridae, it presents a class-I spike complex on its surface that facilitates cell entry. The virus’s cellular receptor is matriglycan, a linear carbohydrate that is present on α-dystroglycan3,4, but the molecular mechanism that LASV uses to recognize this glycan is unknown. In addition, LASV and other arenaviruses have a unique signal peptide that forms an integral and functionally important part of the mature spike5,6,7,8; yet the structure, function and topology of the signal peptide in the membrane remain uncertain9,10,11. Here we solve the structure of a complete native LASV spike complex, finding that the signal peptide crosses the membrane once and that its amino terminus is located in the extracellular region. Together with a double-sided domain-switching mechanism, the signal peptide helps to stabilize the spike complex in its native conformation. This structure reveals that the LASV spike complex is preloaded with matriglycan, suggesting the mechanism of binding and rationalizing receptor recognition by α-dystroglycan-tropic arenaviruses. This discovery further informs us about the mechanism of viral egress and may facilitate the rational design of novel therapeutics that exploit this binding site.

DOI: 10.1038/s41586-022-04429-2

Source: https://www.nature.com/articles/s41586-022-04429-2

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