Autor: |
Jin Xie, Mohamed Ouizougun-Oubari, Li Wang, Guanglei Zhai, Daitze Wu, Zhaohu Lin, Manfu Wang, Barbara Ludeke, Xiaodong Yan, Tobias Nilsson, Lu Gao, Xinyi Huang, Rachel Fearns, Shuai Chen |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024) |
Druh dokumentu: |
article |
ISSN: |
2041-1723 |
DOI: |
10.1038/s41467-024-47470-7 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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