Implications of the HIV-1 Rev dimer structure at 3.2 Å resolution for multimeric binding to the Rev response element

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 13; pp. 5810 - 5814
• Main Authors: DiMattia, Michael A, Watts, Norman R, Stahl, Stephen J, Rader, Christoph, Wingfield, Paul T, Stuart, David I, Steven, Alasdair C, Grimes, Jonathan M
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 30.03.2010; National Acad Sciences
• Subjects: Antibodies, Monoclonal; Binding sites; Biochemistry; Biological Sciences; Cells; Crystal structure; Crystallography, X-Ray; Crystals; Dimerization; Dimers; Genes, env; HIV; HIV 1; HIV Antibodies; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - metabolism; Human immunodeficiency virus; Human immunodeficiency virus 1; hydrophobicity; Immunoglobulin Fab Fragments; messenger RNA; Models, Molecular; Molecular structure; Molecules; Monomers; oligomerization; physiological transport; Protein Binding; Protein Engineering; Protein Structure, Quaternary; Proteins; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; regulatory proteins; rev Gene Products, Human Immunodeficiency Virus - chemistry; rev Gene Products, Human Immunodeficiency Virus - genetics; rev Gene Products, Human Immunodeficiency Virus - immunology; rev Gene Products, Human Immunodeficiency Virus - metabolism; rev genes; Ribonucleic acid; RNA; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0914946107

HIV-1 Rev is a small regulatory protein that mediates the nuclear export of viral mRNAs, an essential step in the HIV replication cycle. In this process Rev oligomerizes in association with a highly structured RNA motif, the Rev response element. Crystallographic studies of Rev have been hampered by the protein's tendency to aggregate, but Rev has now been found to form a stable soluble equimolar complex with a specifically engineered monoclonal Fab fragment. We have determined the structure of this complex at 3.2 Å resolution. It reveals a molecular dimer of Rev, bound on either side by a Fab, where the ordered portion of each Rev monomer (residues 9-65) contains two coplanar α-helices arranged in hairpin fashion. Subunits dimerize through overlapping of the hairpin prongs. Mating of hydrophobic patches on the outer surface of the dimer is likely to promote higher order interactions, suggesting a model for Rev oligomerization onto the viral RNA.