8UFM

Crystal Structure of L516C/Y647C Mutant of SARS-Unique Domain (SUD) from SARS-CoV-2

8UFM の概要

• エントリーDOI: 10.2210/pdb8ufm/pdb
• 分子名称: Papain-like protease nsp3, FORMIC ACID, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: structural genomics, center for structural genomics of infectious diseases, csgid, sud, sars unique domain, center for structural biology of infectious diseases, csbid, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30536.92

構造登録者

Minasov, G.,Shuvalova, L.,Brunzelle, J.S.,Rosas-Lemus, M.,Kiryukhina, O.,Satchell, K.J.F.,Center for Structural Genomics of Infectious Diseases (CSGID),Center for Structural Biology of Infectious Diseases (CSBID) (登録日: 2023-10-04, 公開日: 2023-10-18, 最終更新日: 2025-09-24)

主引用文献

Rosas-Lemus, M.,Minasov, G.,Brunzelle, J.S.,Taha, T.Y.,Lemak, S.,Yin, S.,Shuvalova, L.,Rosecrans, J.,Khanna, K.,Seifert, H.S.,Savchenko, A.,Stogios, P.J.,Ott, M.,Satchell, K.J.F.
Torsional twist of the SARS-CoV and SARS-CoV-2 SUD-N and SUD-M domains.
Protein Sci., 34:e70050-e70050, 2025

PubMed Abstract: Coronavirus non-structural protein 3 (nsp3) forms hexameric crowns of pores in the double membrane vesicle that houses the replication-transcription complex. Nsp3 in SARS-like viruses has three unique domains absent in other coronavirus nsp3 proteins. Two of these, SUD-N (Macrodomain 2) and SUD-M (Macrodomain 3), form two lobes connected by a peptide linker and an interdomain disulfide bridge. We resolve the first complete x-ray structure of SARS-CoV SUD-N/M as well as a mutant variant of SARS-CoV-2 SUD-N/M modified to restore cysteines for interdomain disulfide bond naturally lost by evolution. Comparative analysis of all structures revealed SUD-N and SUD-M are not rigidly associated but rather have significant rotational flexibility. Phylogenetic analysis supports that the potential to form the disulfide bond is common across betacoronavirus isolates from many bat species and civets, but also one or both of the cysteines that form the disulfide bond are absent across isolates from bats and pangolins. The absence of these cysteines does not impact viral replication or protein translation.

PubMed: 39969084
DOI: 10.1002/pro.70050

実験手法

X-RAY DIFFRACTION (1.65 Å)