title: The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.
abstract: The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.
authors.affiliation: Graduate Group in Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: David S
authors.initials: DS
authors.lastname: Booth
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cheng
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 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D012326:RNA Splicing; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / 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; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; 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; D020931:ran GTP-Binding Protein; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C514860:rev protein, Human Immunodeficiency Virus-1
keywords: HIV; RNA export; biophysics; electron microscopy; human; infectious disease; microbiology; structural biology; viruses