Binding of an HIV Rev peptide to Rev responsive element RNA induces formation of purine-purine base pairs.
The Rev responsive element (RRE) is an RNA secondary structural element within the env gene of HIV and is the binding site for the viral Rev protein. Formation of the Rev-RRE complex is involved in regulation of splicing and transport of mRNA from the nucleus. To understand the structural basis for the specific recognition of RRE by Rev, we have studied a model system for this interaction using NMR. We have obtained a specific 1:1 complex between an RNA derived from stem IIB of RRE, which contains the highest affinity Rev binding site, and a modified Rev34-50 peptide, which binds the RRE as an alpha-helix [Tan, R., et al. (1993) Cell 73, 1031-1040]. Binding of the peptide was accompanied by a conformational change in the RNA, which resulted in the formation of additional base pairs not present in the free RNA. Two of these induced base pairs are purine-purine pairs within the internal loop of RRE, which had been previously proposed on the basis of biochemical experiments [Bartel, D.P., et al. (1991) Cell 67, 529-536]. The formation of non-Watson-Crick base pairs, interactions in the major groove, and protein-induced conformational changes may prove to be common characteristics of RNA recognition of proteins.
Battiste
J L
JL
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
Tan
R
R
Frankel
A D
AD
Williamson
J R
JR
D000595:Amino Acid Sequence; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D015694:Gene Products, rev / Q000737:chemistry / Q000378:metabolism*; D006678:HIV / Q000235:genetics / Q000378:metabolism*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011687:Purines; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D010446:Peptide Fragments; D011687:Purines; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus