29qh | pdb_000029qh
Crystal structure of Parechovirus A1 RdRP in out/down conformation
Structural highlights
FunctionPOLG_HPE1H Capsid proteins VP0, VP2, VP3 form a closed capsid enclosing the viral positive strand RNA genome. Capsid proteins interact with host alpha-V/beta-3 integrin heterodimer to provide virion attachment target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis.[1] Protein 2A: Is not a protease. Protein 2B: Affects membrane integrity and cause an increase in membrane permeability. Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor. Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals.[PROSITE-ProRule:PRU00539] Publication Abstract from PubMedParechovirus A1 (PeV A1) 3D(pol) is an RNA-dependent RNA polymerase responsible for replication of the virus genome. We solved crystal structures of PeV A1 3D(pol) structure in complex with GTP and in apo-state at 1.8-2.0 A resolutions. In the 3D(pol)-GTP complex, the conformation of the conserved motif B loop was stabilized by zinc ion coordination by cysteine residues. Apo-state structures of PeV A1 3D(pol) showed significant conformational flexibility in the motif B loop, in the absence of zinc. While one of the conformational states of apo-3D(pol) was similar to the 3D(pol)-GTP complex structure, the alternative apo-3D(pol) conformation showed a 4.3 A movement of the motif B loop out of the active site cavity relative to the complex of 3D(pol) with GTP. We propose that PeV A1 3D(pol) activity is regulated by conformational stabilization of the motif B loop by zinc coordination. Crystal structures of Parechovirus A1 3D(pol) reveal a mechanism of conformational stabilization in +ssRNA virus RNA-dependent RNA polymerase.,Guryanov SG, Mitchell C, Kajander T, Butcher SJ J Struct Biol. 2026 Sep 10;218(4):108370. doi: 10.1016/j.jsb.2026.108370. PMID:42722143[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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