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SARS-CoV-2 刺突蛋白与人波形蛋白结合的理化性质。

Physicochemical Nature of SARS-CoV-2 Spike Protein Binding to Human Vimentin.

机构信息

Independent Laboratory of Nanomedicine, Medical University of Bialystok, PL-15222 Białystok, Poland.

Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, PL-15222 Białystok, Poland.

出版信息

ACS Appl Mater Interfaces. 2023 Jul 19;15(28):34172-34180. doi: 10.1021/acsami.3c03347. Epub 2023 Jul 6.

Abstract

Vimentin, a protein that builds part of the cytoskeleton and is involved in many aspects of cellular function, was recently identified as a cell surface attachment site for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study investigated the physicochemical nature of the binding between the SARS-CoV-2 S1 glycoprotein receptor binding domain (S1 RBD) and human vimentin using atomic force microscopy and a quartz crystal microbalance. The molecular interactions of S1 RBD and vimentin proteins were quantified using vimentin monolayers attached to the cleaved mica or a gold microbalance sensor as well as in its native extracellular form present on the live cell surface. The presence of specific interactions between vimentin and S1 RBD was also confirmed using in silico studies. This work provides new evidence that cell-surface vimentin (CSV) functions as a site for SARS-CoV-2 virus attachment and is involved in the pathogenesis of Covid-19, providing a potential target for therapeutic countermeasures.

摘要

波形蛋白是一种构成细胞骨架的部分,并参与细胞功能的许多方面,最近被确定为严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的细胞表面附着位点。本研究使用原子力显微镜和石英晶体微天平研究了 SARS-CoV-2 S1 糖蛋白受体结合域(S1 RBD)与人类波形蛋白之间结合的物理化学性质。使用附着在切割云母或金微天平传感器上的波形蛋白单层以及存在于活细胞膜表面的天然细胞外形式来定量测量 S1 RBD 和波形蛋白蛋白之间的分子相互作用。还使用计算机模拟研究证实了波形蛋白和 S1 RBD 之间存在特异性相互作用。这项工作提供了新的证据,表明细胞表面波形蛋白(CSV)作为 SARS-CoV-2 病毒附着的位点,并参与了 COVID-19 的发病机制,为治疗对策提供了一个潜在的目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db3a/10360031/b8b5903c4cee/am3c03347_0002.jpg

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