Structural basis for cooperative RNA binding and export complex assembly by HIV Rev.
HIV replication requires nuclear export of unspliced viral RNAs to translate structural proteins and package genomic RNA. Export is mediated by cooperative binding of the Rev protein to the Rev response element (RRE) RNA, to form a highly specific oligomeric ribonucleoprotein (RNP) that binds to the Crm1 host export factor. To understand how protein oligomerization generates cooperativity and specificity for RRE binding, we solved the crystal structure of a Rev dimer at 2.5-Å resolution. The dimer arrangement organizes arginine-rich helices at the ends of a V-shaped assembly to bind adjacent RNA sites and structurally couple dimerization and RNA recognition. A second protein-protein interface arranges higher-order Rev oligomers to act as an adaptor to the host export machinery, with viral RNA bound to one face and Crm1 to another, the oligomers thereby using small, interconnected modules to physically arrange the RNP for efficient export.
Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, California, USA.
Matthew D
MD
Daugherty
Bella
B
Liu
Alan D
AD
Frankel
D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D015497:HIV-1 / Q000502:physiology; D028884:Karyopherins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020218:Response Elements; D016415:Sequence Alignment; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D000097606:Exportin 1 Protein
D028884:Karyopherins; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C514860:rev protein, Human Immunodeficiency Virus-1