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Costabilization of peptide and RNA structure in an HIV Rev peptide-RRE complex.


Biochemistry. 1994 Dec 6;33(48):14579-85. Unique Identifier : AIDSLINE

An arginine-rich peptide corresponding to amino acids 34-50 of the human immunodeficiency virus Rev protein has been shown to bind specifically to its RNA-binding site (RRE) when the peptide is in an alpha-helical conformation. Mutation of any one of six amino acids (Thr34, Arg35, Arg38, Arg39, Asn40, or Arg44) was shown to strongly decrease specific RNA-binding affinity in vitro, suggesting that these residues may contact specific bases or distinct structural features of the RNA. We now show that the four arginine side chains, and not just their charge, are important for specific binding in vivo, and present evidence that three additional arginines (Arg46, Arg48, and Arg50) may make electrostatic contacts to the RRE. RNA-binding specificity of the Rev peptide is temperature-dependent in vitro, correlating with alpha-helix unfolding. Circular dichroism experiments indicate that the peptide helical structure is stabilized when bound specifically to the RRE and that the RNA undergoes a conformational change upon binding. Because the structures of the peptide and RNA in this model system appear to be mutually stabilized upon binding, it is suggested that the entire complex may be viewed as a single folding unit.

Amino Acid Sequence Base Sequence Circular Dichroism Gene Expression Regulation, Viral Gene Products, rev/*METABOLISM Genes, env HIV-1/*METABOLISM In Vitro Molecular Sequence Data Nucleic Acid Conformation Protein Structure, Secondary Regulatory Sequences, Nucleic Acid Ribonucleoproteins/CHEMISTRY RNA, Viral/*METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Temperature JOURNAL ARTICLE


Information in this article was accurate in March 30, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.