Role of the trans-activation response element in dimerization of HIV-1 RNA

Ebbe S Andersen, Sonia Antoranz Contera, Bjarne Knudsen, Christian K Damgaard, Flemming Besenbacher, Jørgen Kjems

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

The HIV-1 genome consists of two identical RNA strands that are linked together through non-covalent interactions. A major determinant for efficient dimerization of the two RNA strands is the interaction between palindromic sequences in the dimerization initiation site. Here we use an interplay of bioinformatics, biochemistry, and atomic force microscopy to describe another conserved palindrome in the trans-activation response element (TAR) that functions as a strong dimerization site when transiently exposed to the viral nucleocapsid protein. In conjunction with the DIS interaction, the TAR dimerization induces the formation of a 65-nm higher-order circular structure in the dimeric HIV-1 RNA. Our results provide a molecular model for the role of TAR in packaging and reverse transcription of the viral genome. The unique structure of the TAR-TAR dimer renders it an intriguing therapeutic target for the treatment of HIV-1 infection.
OriginalsprogEngelsk
TidsskriftJournal of Biological Chemistry
Vol/bind279
Nummer21
Sider (fra-til)22243-22249
Antal sider7
ISSN0021-9258
DOI
StatusUdgivet - 21 maj 2004

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