7V2Z

ZIKV NS3helicase in complex with ssRNA and ATP-Mn2+

Summary for 7V2Z

• Entry DOI: 10.2210/pdb7v2z/pdb
• Descriptor: Core protein, RNA (5'-R(*AP*GP*AP*UP*C)-3'), MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: zikv ns3helicase, viral protein
• Biological source: Zika virus (ZIKV); More
• Total number of polymer chains: 2
• Total formula weight: 51719.74

Authors

Lin, M.M.,Yang, H.T. (deposition date: 2021-08-10, release date: 2022-08-17, Last modification date: 2023-11-29)

Primary citation

Lin, M.,Cui, W.,Tian, H.,Zhang, Y.,Chen, C.,Yang, X.,Chi, H.,Mu, Z.,Chen, C.,Wang, Z.,Ji, X.,Yang, H.,Lin, Z.
Structural Basis of Zika Virus Helicase in RNA Unwinding and ATP Hydrolysis.
Acs Infect Dis., 8:150-158, 2022

PubMed Abstract: The flavivirus nonstructural protein 3 helicase (NS3hel) is a multifunctional domain protein that is associated with DNA/RNA helicase, nucleoside triphosphatase (NTPase), and RNA 5'-triphosphatase (RTPase) activities. As an NTPase-dependent superfamily 2 (SF2) member, NS3hel employs an NTP-driven motor force to unwind double-stranded RNA while translocating along single-stranded RNA and is extensively involved in the viral replication process. Although the structures of SF2 helicases are widely investigated as promising drug targets, the mechanism of energy transduction between NTP hydrolysis and the RNA binding sites in ZIKV NS3hel remains elusive. Here, we report the crystal structure of ZIKV NS3hel in complex with its natural substrates ATP-Mn and ssRNA. Distinct from other members of the genus, ssRNA binding to ZIKV NS3hel induces relocation of the active water molecules and ATP-associated metal ions in the NTP hydrolysis active site, which promotes the hydrolysis of ATP and the production of AMP. Our findings highlight the importance of the allosteric role of ssRNA on the modulation of ATP hydrolysis and energy utilization.

PubMed: 34904824
DOI: 10.1021/acsinfecdis.1c00455

Experimental method

X-RAY DIFFRACTION (2.10101667251 Å)