8EKE

Cryo-EM structure of SARS CoV-2 Mpro WT protease

8EKE の概要

• エントリーDOI: 10.2210/pdb8eke/pdb
• EMDBエントリー: 28200
• 分子名称: 3C-like proteinase nsp5 (1 entity in total)
• 機能のキーワード: main protease, mpro, sars cov-2, polyprotein, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 2019-nCoV, COVID-19 virus)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67586.96

構造登録者

Narwal, M.,Edwards, T.,Armache, J.P.,Murakami, K.S. (登録日: 2022-09-20, 公開日: 2023-04-26, 最終更新日: 2024-06-19)

主引用文献

Narwal, M.,Armache, J.P.,Edwards, T.J.,Murakami, K.S.
SARS-CoV-2 polyprotein substrate regulates the stepwise M pro cleavage reaction.
J.Biol.Chem., 299:104697-104697, 2023

PubMed Abstract: The processing of the Coronavirus polyproteins pp1a and pp1ab by the main protease M to produce mature proteins is a crucial event in virus replication and a promising target for antiviral drug development. M cleaves polyproteins in a defined order, but how M and/or the polyproteins determine the order of cleavage remains enigmatic due to a lack of structural information about polyprotein-bound M. Here, we present the cryo-EM structures of SARS-CoV-2 M in an apo form and in complex with the nsp7-10 region of the pp1a polyprotein. The complex structure shows that M interacts with only the recognition site residues between nsp9 and nsp10, without any association with the rest of the polyprotein. Comparison between the apo form and polyprotein-bound structures of M highlights the flexible nature of the active site region of M, which allows it to accommodate ten recognition sites found in the polyprotein. These observations suggest that the role of M in selecting a preferred cleavage site is limited and underscores the roles of the structure, conformation, and/or dynamics of the polyproteins in determining the sequence of polyprotein cleavage by M.

PubMed: 37044215
DOI: 10.1016/j.jbc.2023.104697

実験手法

ELECTRON MICROSCOPY (3.36 Å)