2OIY

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

(2010) Nucleic Acids Res 38: 5807-5816

• PubMed: 20460458 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1093/nar/gkq344
• Primary Citation of Related Structures:  
  2OIY, 2OJ0


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

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.