title: Guanine-nucleotide exchange factor RCC1 facilitates a tight binding between the encephalomyocarditis virus leader and cellular Ran GTPase.
abstract: The leader (L) protein of encephalomyocarditis virus (EMCV) shuts off host cell nucleocytoplasmic trafficking (NCT) by inducing hyperphosphorylation of nuclear pore proteins. This dramatic effect by a nonenzymatic protein of 6 kDa is not well understood but clearly involves L binding to cellular Ran GTPase, a critical factor of active NCT. Exogenous GDP and GTP are inhibitory to L-Ran binding, but the guanine-nucleotide exchange factor RCC1 can relieve this inhibition. In the presence of RCC1, L binds Ran with a KD (equilibrium dissociation constant) of ≈ 3 nM and reaches saturation within 20 min. The results of fluorescently tagged nucleotide experiments suggest that L-Ran interactions affect the nucleotide-binding pocket of Ran.
authors.affiliation: Department of Biochemistry, Institute for Molecular Virology, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Ryan V
authors.initials: RV
authors.lastname: Petty
authors.forename: Ann C
authors.initials: AC
authors.lastname: Palmenberg
mesh_terms: D018188:Cardiovirus Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007700:Kinetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C062521:RCC1 protein, human; D014764:Viral Proteins; D020931:ran GTP-Binding Protein
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