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.
Keywords:
HIV; biochemistry; infectious disease; microbiology; nuclear export; protein-RNA structure; viruses.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Binding Sites
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Cell Line, Tumor
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Cell Nucleus / metabolism
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Cell Nucleus / virology
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Crystallography, X-Ray
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Cytosol / metabolism
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Cytosol / virology
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Exportin 1 Protein
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Gene Expression Regulation
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HEK293 Cells
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HIV-1 / genetics*
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HIV-1 / metabolism
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HeLa Cells
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Host-Pathogen Interactions
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Humans
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Karyopherins / genetics
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Karyopherins / metabolism
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Models, Molecular
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Protein Binding
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RNA Splicing
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RNA, Viral / chemistry
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RNA, Viral / genetics*
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RNA, Viral / metabolism
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Response Elements*
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Signal Transduction
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T-Lymphocytes / metabolism
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T-Lymphocytes / virology
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Virus Replication / genetics*
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rev Gene Products, Human Immunodeficiency Virus / chemistry
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rev Gene Products, Human Immunodeficiency Virus / genetics*
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rev Gene Products, Human Immunodeficiency Virus / metabolism
Substances
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Karyopherins
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RNA, Viral
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Receptors, Cytoplasmic and Nuclear
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Recombinant Proteins
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rev Gene Products, Human Immunodeficiency Virus
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rev protein, Human Immunodeficiency Virus-1