8ZE4

MPXV mRNA cap N7 methyltransferase mutant-H122D

8ZE4 の概要

• エントリーDOI: 10.2210/pdb8ze4/pdb
• 分子名称: mRNA-capping enzyme catalytic subunit, mRNA-capping enzyme regulatory subunit OPG124, S-ADENOSYLMETHIONINE (3 entities in total)
• 機能のキーワード: complex, transferase
• 由来する生物種: Monkeypox virus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68530.57

構造登録者

Chen, A.k.,Li, J.X. (登録日: 2024-05-04, 公開日: 2025-03-12)

主引用文献

Chen, A.,Fang, N.,Zhang, Z.,Wen, Y.,Shen, Y.,Zhang, Y.,Zhang, L.,Zhao, G.,Ding, J.,Li, J.
Structural basis of the monkeypox virus mRNA cap N7 methyltransferase complex.
Emerg Microbes Infect, 13:2369193-2369193, 2024

PubMed Abstract: The global outbreak of Mpox, caused by the monkeypox virus (MPXV), has attracted international attention and become another major infectious disease event after COVID-19. The mRNA cap N7 methyltransferase (RNMT) of MPXV methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs and plays a vital role in evading host antiviral immunity. MPXV RNMT is composed of the large subunit E1 and the small subunit E12. How E1 and E12 of MPXV assembly remains unclear. Here, we report the crystal structures of E12, the MTase domain of E1 with E12 (E1-E12) complex, and the E1-E12-SAM ternary complex, revealing the detailed conformations of critical residues and the structural changes upon E12 binding to E1. Functional studies suggest that E1 N-terminal extension (Asp545-Arg562) and the small subunit E12 play an essential role in the binding process of SAM. Structural comparison of the AlphaFold2-predicted E1, E1-E12 complex, and the homologous D1-D12 complex of vaccinia virus (VACV) indicates an allosteric activating effect of E1 in MPXV. Our findings provide the structural basis for the MTase activity stimulation of the E1-E12 complex and suggest a potential interface for screening the anti-poxvirus inhibitors.

PubMed: 38873898
DOI: 10.1080/22221751.2024.2369193

実験手法

X-RAY DIFFRACTION (3.33 Å)