5ls4 | pdb_00005ls4
Mopeia virus exonuclease domain complexed with Calcium
Structural highlights
Function[Q5S581_MOPEI] Encapsidates the genome, protecting it from nucleases. The encapsidated genomic RNA is termed the nucleocapsid (NC). Serves as template for viral transcription and replication. The increased presence of protein N in host cell does not seem to trigger the switch from transcription to replication as observed in other negative strain RNA viruses.[PIRNR:PIRNR004029] Publication Abstract from PubMedThe Arenaviridae family is one of the two RNA viral families that encode a 3'-5' exonuclease in their genome. An exonuclease domain is found in the Arenaviridae nucleoprotein and targets dsRNA specifically. This domain is directly involved in suppression of innate immunity in the host cell. Like most phosphate-processing enzymes, it requires a divalent metal ion such as Mg2+ (or Mn2+) as a cofactor to catalyse nucleotide-cleavage and nucleotide-transfer reactions. On the other hand, calcium (Ca2+) inhibits this enzymatic activity, in spite of the fact that Mg2+ and Ca2+ present comparable binding affinities and biological availabilities. Here, the molecular and structural effects of the replacement of magnesium by calcium and its inhibition mechanism for phosphodiester cleavage, an essential reaction in the viral process of innate immunity suppression, are studied. Biochemical data and high-resolution structures of the Mopeia virus exonuclease domain complexed with each ion are reported for the first time. The consequences of the ion swap for the stability of the protein, the catalytic site and the functional role of a specific metal ion in enabling the catalytic cleavage of a dsRNA substrate are outlined. Activity inhibition and crystal polymorphism induced by active-site metal swapping.,Yekwa E, Khourieh J, Canard B, Papageorgiou N, Ferron F Acta Crystallogr D Struct Biol. 2017 Aug 1;73(Pt 8):641-649. doi:, 10.1107/S205979831700866X. Epub 2017 Jul 28. PMID:28777079[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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