8KDC

Cryo-EM structure of the human parainfluenza virus hPIV3 L-P polymerase in monomeric form

8KDC の概要

• エントリーDOI: 10.2210/pdb8kdc/pdb
• EMDBエントリー: 37131
• 分子名称: RNA-directed RNA polymerase L, Phosphoprotein, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: dimeric polymerase, parainfluenza virus, l-p polymerase, cryo-em structure, non-segmented negative-strand rna virus, l-l dimerization, rna replication, rdrp active site, viral protein
• 由来する生物種: Human respirovirus 3; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 602615.39

構造登録者

Xie, J.,Wang, L.,Zhai, G.,Wu, D.,Lin, Z.,Wang, M.,Yan, X.,Gao, L.,Huang, X.,Fearns, R.,Chen, S. (登録日: 2023-08-09, 公開日: 2024-04-24)

主引用文献

Xie, J.,Ouizougun-Oubari, M.,Wang, L.,Zhai, G.,Wu, D.,Lin, Z.,Wang, M.,Ludeke, B.,Yan, X.,Nilsson, T.,Gao, L.,Huang, X.,Fearns, R.,Chen, S.
Structural basis for dimerization of a paramyxovirus polymerase complex.
Nat Commun, 15:3163-3163, 2024

PubMed Abstract: The transcription and replication processes of non-segmented, negative-strand RNA viruses (nsNSVs) are catalyzed by a multi-functional polymerase complex composed of the large protein (L) and a cofactor protein, such as phosphoprotein (P). Previous studies have shown that the nsNSV polymerase can adopt a dimeric form, however, the structure of the dimer and its function are poorly understood. Here we determine a 2.7 Å cryo-EM structure of human parainfluenza virus type 3 (hPIV3) L-P complex with the connector domain (CD') of a second L built, while reconstruction of the rest of the second L-P obtains a low-resolution map of the ring-like L core region. This study reveals detailed atomic features of nsNSV polymerase active site and distinct conformation of hPIV3 L with a unique β-strand latch. Furthermore, we report the structural basis of L-L dimerization, with CD' located at the putative template entry of the adjoining L. Disruption of the L-L interface causes a defect in RNA replication that can be overcome by complementation, demonstrating that L dimerization is necessary for hPIV3 genome replication. These findings provide further insight into how nsNSV polymerases perform their functions, and suggest a new avenue for rational drug design.

PubMed: 38605025
DOI: 10.1038/s41467-024-47470-7

実験手法

ELECTRON MICROSCOPY (3.3 Å)