Deep penetration of an alpha-helix into a widened RNA major groove in the HIV-1 rev peptide-RNA aptamer complex.
A combined NMR-molecular dynamics approach has been applied to determine the solution structure of a HIV-1 17-mer rev peptide bound to its 35-mer high affinity RNA aptamer binding site. Complex formation involves adaptive binding with the alpha-helical arginine-rich basic rev peptide targeting a widened RNA major groove centred about adjacent G.A and reversed A.A mismatches. We have also identified a U AU triple in the aptamer complex with the Hoogsteen-paired uracil base sandwiched between two arginine side chains. The intermolecular contacts identified in the aptamer complex readily account for the consequences of peptide and RNA mutations, as well as the results of previous in vitro selection experiments. The details of molecular recognition associated with targeting by rev of its high affinity RNA binding sites open new opportunities for structure-based drug design strategies.
Ye
X
X
Cellular Biochemistry and Biophysics Program Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Gorin
A
A
Ellington
A D
AD
Patel
D J
DJ
D000595:Amino Acid Sequence; D015694:Gene Products, rev / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012367:RNA, Viral / Q000737:chemistry*; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D010455:Peptides; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus