9C45

SARS-CoV-2 S + S2L20 (local refinement of NTD and S2L20 Fab variable region)

9C45 の概要

• エントリーDOI: 10.2210/pdb9c45/pdb
• EMDBエントリー: 45174 45175
• 分子名称: S2L20 Fab Light Chain Variable Region, S2L20 Fab Heavy Chain Variable, Spike glycoprotein, ... (6 entities in total)
• 機能のキーワード: s2l20, s, ntd, rbd, coronavirus, covid-19, sars-cov-2, hexapro, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 169606.31

構造登録者

McCallum, M.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2024-06-03, 公開日: 2024-11-20, 最終更新日: 2024-12-11)

主引用文献

Liu, P.,Huang, M.L.,Guo, H.,McCallum, M.,Si, J.Y.,Chen, Y.M.,Wang, C.L.,Yu, X.,Shi, L.L.,Xiong, Q.,Ma, C.B.,Bowen, J.E.,Tong, F.,Liu, C.,Sun, Y.H.,Yang, X.,Chen, J.,Guo, M.,Li, J.,Corti, D.,Veesler, D.,Shi, Z.L.,Yan, H.
Design of customized coronavirus receptors.
Nature, 635:978-986, 2024

PubMed Abstract: Although coronaviruses use diverse receptors, the characterization of coronaviruses with unknown receptors has been impeded by a lack of infection models. Here we introduce a strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building artificial receptor scaffolds comprising various modules and generating specific virus-binding domains. We identify key factors for CVRs to functionally mimic native receptors by facilitating spike proteolytic cleavage, membrane fusion, pseudovirus entry and propagation for various coronaviruses. We delineate functional SARS-CoV-2 spike receptor-binding sites for CVR design and reveal the mechanism of cell entry promoted by the N-terminal domain-targeting S2L20-CVR. We generated CVR-expressing cells for 12 representative coronaviruses from 6 subgenera, most of which lack known receptors, and show that a pan-sarbecovirus CVR supports propagation of a propagation-competent HKU3 pseudovirus and of authentic RsHuB2019A. Using an HKU5-specific CVR, we successfully rescued wild-type and ZsGreen-HiBiT-incorporated HKU5-1 (LMH03f) and isolated a HKU5 strain from bat samples. Our study demonstrates the potential of the CVR strategy for establishing native receptor-independent infection models, providing a tool for studying viruses that lack known susceptible target cells.

PubMed: 39478224
DOI: 10.1038/s41586-024-08121-5

実験手法

ELECTRON MICROSCOPY (3.2 Å)