5wx1

The closed-conformation crystal structure of the full-length pestivirus NS3 with its NS4A protease cofactor segment

spinqualitylabelsall models 5wx1, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5wx1 is a 1 chain structure with sequence from Classical swine fever virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5U8X5_9FLAV Publication Abstract from PubMed The nonstructural protein NS3 from the Flaviviridae family is a multi-functional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the Classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at 2.35 A resolution. The structure reveals a previously unidentified approximately 2200-A2 intra-molecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the NS3-NS4A cis-cleavage event. Although this conformation is incompatible with protease trans-cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo Collectively, our work reveals important features of protease-helicase coordination in pestivirus NS3, and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein.IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are quite unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis-cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through different conformational states. The uncoupling of protease trans-cleavage and helicase activities in the pestivirus NS3.,Zheng F, Lu G, Li L, Gong P, Pan Z J Virol. 2017 Aug 23. pii: JVI.01094-17. doi: 10.1128/JVI.01094-17. PMID:28835495 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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