4CBM

Pestivirus NS3 helicase

Summary for 4CBM

• Entry DOI: 10.2210/pdb4cbm/pdb
• Related: 4CBG 4CBH 4CBI 4CBL
• Descriptor: SERINE PROTEASE NS3 (2 entities in total)
• Functional Keywords: hydrolase, sf2 helicases, flaviviridae ns3, saxs
• Biological source: CLASSICAL SWINE FEVER VIRUS
• Cellular location: E(rns) glycoprotein: Host membrane; Peripheral membrane protein. Envelope glycoprotein E2: Host cell surface . Cysteine protease NS2: Host membrane ; Multi-pass membrane protein : P19712
• Total number of polymer chains: 4
• Total formula weight: 232096.34

Authors

Tortorici, M.A.,Duquerroy, S.,Kwok, J.,Vonrhein, C.,Perez, J.,Lamp, B.,Bricogne, G.,Rumenapf, T.,Vachette, P.,Rey, F.A. (deposition date: 2013-10-14, release date: 2015-01-21, Last modification date: 2023-12-20)

Primary citation

Tortorici, M.A.,Duquerroy, S.,Kwok, J.,Vonrhein, C.,Perez, J.,Lamp, B.,Bricogne, G.,Rumenapf, T.,Vachette, P.,Rey, F.A.
X-Ray Structure of the Pestivirus Ns3 Helicase and its Conformation in Solution.
J.Virol., 89:4356-, 2015

PubMed Abstract: Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of nonstructural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-Å resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as it contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses from which the core protein is deleted map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with the findings of small-angle X-ray-scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a nonhydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication.

PubMed: 25653438
DOI: 10.1128/JVI.03165-14

Experimental method

X-RAY DIFFRACTION (3.27 Å)