2JLY

Dengue virus 4 NS3 helicase in complex with ssRNA and ADP-Phosphate

Summary for 2JLY

• Entry DOI: 10.2210/pdb2jly/pdb
• Related: 2JLQ 2JLR 2JLS 2JLU 2JLV 2JLW 2JLX 2JLZ
• Descriptor: SERINE PROTEASE SUBUNIT NS3, 5'-R(*AP*GP*AP*CP*UP*AP*AP*CP*AP*AP*CP*U)-3', ADENOSINE-5'-DIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: hydrolase-rna complex, envelope protein, ribonucleoprotein, capsid protein, rna replication, serine protease, glycoprotein, dengue virus, metal-binding, transferase, atp-binding, rna-binding, flaviviruses, transcription regulation, rna-directed rna polymerase, nucleotide-binding, viral nucleoprotein, secreted, helicase, protease, hydrolase, phosphate, cleavage on pair of basic residues, endoplasmic reticulum, nucleotidyltransferase, adp, ssrna, virion, atpase, nucleus, membrane, transmembrane, transcription, phosphoprotein, ns3 helicase structure, multifunctional enzyme, hydrolase/rna
• Biological source: DENGUE VIRUS 4
• Cellular location: Capsid protein C: Virion (Potential). Peptide pr: Secreted (By similarity). Small envelope protein M: Virion membrane; Multi-pass membrane protein (By similarity). Envelope protein E: Virion membrane; Multi- pass membrane protein (By similarity). Non-structural protein 1: Secreted. Non-structural protein 2A-alpha: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): Q2YHF0
• Total number of polymer chains: 4
• Total formula weight: 111620.03

Authors

Luo, D.H.,Xu, T.,Watson, R.P.,Becker, D.S.,Sampath, A.,Jahnke, W.,Yeong, S.S.,Wang, C.H.,Lim, S.P.,Vasudevan, S.G.,Lescar, J. (deposition date: 2008-09-15, release date: 2008-11-25, Last modification date: 2023-12-13)

Primary citation

Luo, D.,Xu, T.,Watson, R.P.,Scherer-Becker, D.,Sampath, A.,Jahnke, W.,Yeong, S.S.,Wang, C.H.,Lim, S.P.,Strongin, A.,Vasudevan, S.G.,Lescar, J.
Insights Into RNA Unwinding and ATP Hydrolysis by the Flavivirus Ns3 Protein.
Embo J., 27:3209-, 2008

PubMed Abstract: Together with the NS5 polymerase, the NS3 helicase has a pivotal function in flavivirus RNA replication and constitutes an important drug target. We captured the dengue virus NS3 helicase at several stages along the catalytic pathway including bound to single-stranded (ss) RNA, to an ATP analogue, to a transition-state analogue and to ATP hydrolysis products. RNA recognition appears largely sequence independent in a way remarkably similar to eukaryotic DEAD box proteins Vasa and eIF4AIII. On ssRNA binding, the NS3 enzyme switches to a catalytic-competent state imparted by an inward movement of the P-loop, interdomain closure and a change in the divalent metal coordination shell, providing a structural basis for RNA-stimulated ATP hydrolysis. These structures demonstrate for the first time large quaternary changes in the flaviviridae helicase, identify the catalytic water molecule and point to a beta-hairpin that protrudes from subdomain 2, as a critical element for dsRNA unwinding. They also suggest how NS3 could exert an effect as an RNA-anchoring device and thus participate both in flavivirus RNA replication and assembly.

PubMed: 19008861
DOI: 10.1038/EMBOJ.2008.232

Experimental method

X-RAY DIFFRACTION (2.4 Å)