5CCV

Crystal structure of full-length NS5 from dengue virus type 3

Summary for 5CCV

• Entry DOI: 10.2210/pdb5ccv/pdb
• Descriptor: RNA-directed RNA polymerase NS5, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: methyltransferase, nonstructural protein, transferase
• Biological source: Dengue virus type 3 (DENV-3)
• Cellular location: Capsid protein C: Virion . Peptide pr: Secreted . Small envelope protein M: Virion membrane ; Multi-pass membrane protein . Envelope protein E: Virion membrane ; Multi-pass membrane protein . Non-structural protein 1: Secreted. Non-structural protein 2A: Host endoplasmic reticulum membrane ; Multi- pass membrane protein . Serine protease subunit NS2B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Multi- pass membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi- pass membrane protein . RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P27915
• Total number of polymer chains: 8
• Total formula weight: 837241.70

Authors

Klema, V.J.,Choi, K.H. (deposition date: 2015-07-02, release date: 2016-02-03, Last modification date: 2023-09-27)

Primary citation

Klema, V.J.,Ye, M.,Hindupur, A.,Teramoto, T.,Gottipati, K.,Padmanabhan, R.,Choi, K.H.
Dengue Virus Nonstructural Protein 5 (NS5) Assembles into a Dimer with a Unique Methyltransferase and Polymerase Interface.
Plos Pathog., 12:e1005451-e1005451, 2016

PubMed Abstract: Flavivirus nonstructural protein 5 (NS5) consists of methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, which catalyze 5'-RNA capping/methylation and RNA synthesis, respectively, during viral genome replication. Although the crystal structure of flavivirus NS5 is known, no data about the quaternary organization of the functional enzyme are available. We report the crystal structure of dengue virus full-length NS5, where eight molecules of NS5 are arranged as four independent dimers in the crystallographic asymmetric unit. The relative orientation of each monomer within the dimer, as well as the orientations of the MTase and RdRp domains within each monomer, is conserved, suggesting that these structural arrangements represent the biologically relevant conformation and assembly of this multi-functional enzyme. Essential interactions between MTase and RdRp domains are maintained in the NS5 dimer via inter-molecular interactions, providing evidence that flavivirus NS5 can adopt multiple conformations while preserving necessary interactions between the MTase and RdRp domains. Furthermore, many NS5 residues that reduce viral replication are located at either the inter-domain interface within a monomer or at the inter-molecular interface within the dimer. Hence the X-ray structure of NS5 presented here suggests that MTase and RdRp activities could be coordinated as a dimer during viral genome replication.

PubMed: 26895240
DOI: 10.1371/journal.ppat.1005451

Experimental method

X-RAY DIFFRACTION (3.6 Å)