RNA-directed remodeling of the HIV-1 protein Rev orchestrates assembly of the Rev-Rev response element complex.
The HIV-1 protein Rev controls a critical step in viral replication by mediating the nuclear export of unspliced and singly-spliced viral mRNAs. Multiple Rev subunits assemble on the Rev Response Element (RRE), a structured region present in these RNAs, and direct their export through the Crm1 pathway. Rev-RRE assembly occurs via several Rev oligomerization and RNA-binding steps, but how these steps are coordinated to form an export-competent complex is unclear. Here, we report the first crystal structure of a Rev dimer-RRE complex, revealing a dramatic rearrangement of the Rev-dimer upon RRE binding through re-packing of its hydrophobic protein-protein interface. Rev-RNA recognition relies on sequence-specific contacts at the well-characterized IIB site and local RNA architecture at the second site. The structure supports a model in which the RRE utilizes the inherent plasticity of Rev subunit interfaces to guide the formation of a functional complex.
['Jayaraman|Bhargavi|B|', 'Crosby|David C|DC|', 'Homer|Christina|C|', 'Ribeiro|Isabel|I|', 'Mavor|David|D|', 'Frankel|Alan D|AD|']
D021581:Active Transport, Cell Nucleus D001665:Binding Sites D045744:Cell Line, Tumor D002467:Cell Nucleus D018360:Crystallography, X-Ray D003600:Cytosol D004926:Escherichia coli D005786:Gene Expression Regulation D057809:HEK293 Cells D015497:HIV-1 D006367:HeLa Cells D054884:Host-Pathogen Interactions D006801:Humans D028884:Karyopherins D008958:Models, Molecular D011485:Protein Binding D012326:RNA Splicing D012367:RNA, Viral D018160:Receptors, Cytoplasmic and Nuclear D011994:Recombinant Proteins D020218:Response Elements D015398:Signal Transduction D013601:T-Lymphocytes D014779:Virus Replication D054321:rev Gene Products, Human Immunodeficiency Virus
nuclear export HIV biochemistry infectious disease microbiology protein-RNA structure viruses