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Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases.

ABSTRACT: De novo viral RNA-dependent RNA polymerases (RdRPs) utilize their priming element (PE) to facilitate accurate initiation. Upon transition to elongation, the PE has to retreat from the active site to give room to the template-product RNA duplex. However, PE conformational change upon this transition and the role of PE at elongation both remain elusive. Here, we report crystal structures of RdRP elongation complex (EC) from dengue virus serotype 2 (DENV2), demonstrating a dramatic refolding of PE that allows establishment of interactions with the RNA duplex backbone approved to be essential for EC stability. Enzymology data from both DENV2 and hepatitis C virus (HCV) RdRPs suggest that critical transition of the refolding likely occurs after synthesis of a 4- to 5-nucleotide (nt) product together providing a key basis in understanding viral RdRP transition from initiation to elongation.

SUBMITTER: Wu J

PROVIDER: S-EPMC9910504 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases.

Wu Jiqin J Wang Xinyu X Liu Qiaojie Q Lu Guoliang G Gong Peng P

Proceedings of the National Academy of Sciences of the United States of America 20221228 1

De novo viral RNA-dependent RNA polymerases (RdRPs) utilize their priming element (PE) to facilitate accurate initiation. Upon transition to elongation, the PE has to retreat from the active site to give room to the template-product RNA duplex. However, PE conformational change upon this transition and the role of PE at elongation both remain elusive. Here, we report crystal structures of RdRP elongation complex (EC) from dengue virus serotype 2 (DENV2), demonstrating a dramatic refolding of PE ...[more]

PMID: 36577062

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