Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site.
The crystal structure of subtype-B HIV-1 genomic RNA Dimerization Initiation Site duplex revealed chain cleavage at a specific position resulting in 3'-phosphate and 5'-hydroxyl termini. A crystallographic analysis showed that Ba(2+), Mn(2+), Co(2+) and Zn(2+) bind specifically on a guanine base close to the cleaved position. The crystal structures also point to a necessary conformational change to induce an 'in-line' geometry at the cleavage site. In solution, divalent cations increased the rate of cleavage with pH/pKa compensation, indicating that a cation-bound hydroxide anion is responsible for the cleavage. We propose a 'Trojan horse' mechanism, possibly of general interest, wherein a doubly charged cation hosted near the cleavage site as a 'harmless' species is further transformed in situ into an 'aggressive' species carrying a hydroxide anion.
Ennifar
Eric
E
Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire du CNRS, 15 rue René Descartes F-67084 Strasbourg, France.
Walter
Philippe
P
Dumas
Philippe
P
D001665:Binding Sites; D002413:Cations, Divalent / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D015497:HIV-1 / Q000235:genetics*; D008958:Models, Molecular; D012330:RNA, Double-Stranded / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D002413:Cations, Divalent; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D014867:Water
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