2023-05-30 ペンシルベニア州立大学(PennState)
◆そこで、ペンシルベニア州立大学の研究チームが、このプロセスの最も詳細な画像を作成しました。これにより、これらのタンパク質はタンパク質の構造によって指示される一貫した順序で分割されることが明らかになりました。この研究結果は、COVID-19の治療に効果的な薬の開発を支援する可能性があります。
<関連情報>
- https://www.psu.edu/news/eberly-college-science/story/essential-process-sars-cov-2-viral-replication-visualized/
- https://www.jbc.org/article/S0021-9258(23)00339-3/fulltext
SARS-CoV-2ポリタンパク質の基質がMproの段階的切断反応を制御していることが判明
SARS-CoV-2 polyprotein substrate regulates the stepwise Mpro cleavage reaction
Manju Narwal,Jean-Paul Armache,Thomas J. Edwards,Katsuhiko S. Murakami
Journal of Biological Chemistry Received: February 15, 2023
DOI:https://doi.org/10.1016/j.jbc.2023.104697
The processing of the Coronavirus polyproteins pp1a and pp1ab by the main protease Mpro to produce mature proteins is a crucial event in virus replication and a promising target for antiviral drug development. Mpro cleaves polyproteins in a defined order, but how Mpro and/or the polyproteins determine the order of cleavage remains enigmatic due to a lack of structural information about polyprotein-bound Mpro. Here, we present the cryo-EM structures of SARS-CoV-2 Mpro in an apo form and in complex with the nsp7-10 region of the pp1a polyprotein. The complex structure shows that Mpro 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 Mpro highlights the flexible nature of the active site region of Mpro, which allows it to accommodate ten recognition sites found in the polyprotein. These observations suggest that the role of Mpro 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 Mpro.
