Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.
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 A 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 alpha-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.
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford OX3 7BN, UK.
Michael A
MA
DiMattia
Norman R
NR
Watts
Stephen J
SJ
Stahl
Christoph
C
Rader
Paul T
PT
Wingfield
David I
DI
Stuart
Alasdair C
AC
Steven
Jonathan M
JM
Grimes
D000911:Antibodies, Monoclonal; D018360:Crystallography, X-Ray; D019281:Dimerization; D015752:Genes, env; D015483:HIV Antibodies; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments; D008958:Models, Molecular; D011485:Protein Binding; D015202:Protein Engineering; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1