title: RNA-directed remodeling of the HIV-1 protein Rev orchestrates assembly of the Rev-Rev response element complex.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Jayaraman
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Crosby
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Homer
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ribeiro
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: David
authors.initials: D
authors.lastname: Mavor
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Frankel
mesh_terms: D021581:Active Transport, Cell Nucleus; D001665:Binding Sites; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000378:metabolism / Q000821:virology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D012326:RNA Splicing; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000235:genetics*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C514860:rev protein, Human Immunodeficiency Virus-1
keywords: HIV; biochemistry; infectious disease; microbiology; nuclear export; protein-RNA structure; viruses