Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nucleic Acids Research Année : 2010

Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site.

Résumé

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.

Dates et versions

hal-00484372 , version 1 (18-05-2010)

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Citer

Eric Ennifar, Philippe Walter, Philippe Dumas. Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site.. Nucleic Acids Research, 2010, epub ahead of print. ⟨10.1093/nar/gkq344⟩. ⟨hal-00484372⟩

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