7XD8

Crystal Structure of Dengue Virus Serotype 2 (DENV2) Polymerase Elongation Complex (Native Form)

Summary for 7XD8

• Entry DOI: 10.2210/pdb7xd8/pdb
• Descriptor: NS5, RNA (30-mer), RNA (9-mer), ... (6 entities in total)
• Functional Keywords: rna-dependent rna polymerase, de novo synthesis, elongation complex, priming element, transferase, transferase-rna complex, transferase/rna
• Biological source: Dengue virus 2; More
• Total number of polymer chains: 18
• Total formula weight: 526922.46

Authors

Wu, J.,Wang, X.,Gong, P. (deposition date: 2022-03-26, release date: 2022-12-21, Last modification date: 2023-11-29)

Primary citation

Wu, J.,Wang, X.,Liu, Q.,Lu, G.,Gong, P.
Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases.
Proc.Natl.Acad.Sci.USA, 120:e2211425120-e2211425120, 2023

PubMed 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.

PubMed: 36577062
DOI: 10.1073/pnas.2211425120

Experimental method

X-RAY DIFFRACTION (2.85 Å)