7DIY

Crystal structure of SARS-CoV-2 nsp10 bound to nsp14-exoribonuclease domain

7DIY の概要

• エントリーDOI: 10.2210/pdb7diy/pdb
• 分子名称: nsp10 protein, nsp14-ExoN protein, ZINC ION, ... (5 entities in total)
• 機能のキーワード: exoribonuclease, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48492.29

構造登録者

Lin, S.,Chen, H.,Chen, Z.M.,Yang, F.L.,Ye, F.,Zheng, Y.,Yang, J.,Lin, X.,Sun, H.L.,Wang, L.L.,Wen, A.,Cao, Y.,Lu, G.W. (登録日: 2020-11-19, 公開日: 2021-05-19, 最終更新日: 2023-11-29)

主引用文献

Lin, S.,Chen, H.,Chen, Z.,Yang, F.,Ye, F.,Zheng, Y.,Yang, J.,Lin, X.,Sun, H.,Wang, L.,Wen, A.,Dong, H.,Xiao, Q.,Deng, D.,Cao, Y.,Lu, G.
Crystal structure of SARS-CoV-2 nsp10 bound to nsp14-ExoN domain reveals an exoribonuclease with both structural and functional integrity.
Nucleic Acids Res., 49:5382-5392, 2021

PubMed Abstract: The emergence of SARS-CoV-2 infection has posed unprecedented threat to global public health. The virus-encoded non-structural protein 14 (nsp14) is a bi-functional enzyme consisting of an exoribonuclease (ExoN) domain and a methyltransferase (MTase) domain and plays a pivotal role in viral replication. Here, we report the structure of SARS-CoV-2 nsp14-ExoN domain bound to its co-factor nsp10 and show that, compared to the SARS-CoV nsp10/nsp14-full-length complex, SARS-CoV-2 nsp14-ExoN retains an integral exoribonuclease fold and preserves an active configuration in the catalytic center. Analysis of the nsp10/nsp14-ExoN interface reveals a footprint in nsp10 extensively overlapping with that observed in the nsp10/nsp16 structure. A marked difference in the co-factor when engaging nsp14 and nsp16 lies in helix-α1', which is further experimentally ascertained to be involved in nsp14-binding but not in nsp16-engagement. Finally, we also show that nsp10/nsp14-ExoN is enzymatically active despite the absence of nsp14-MTase domain. These data demonstrate that SARS-CoV-2 nsp10/nsp14-ExoN functions as an exoribonuclease with both structural and functional integrity.

PubMed: 33956156
DOI: 10.1093/nar/gkab320

実験手法

X-RAY DIFFRACTION (2.693 Å)