Cardiovirus Leader proteins bind exportins: Implications for virus replication and nucleocytoplasmic trafficking inhibition

Journal Article · Fri Jan 15 04:00:00 EST 2016 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2015.10.001· OSTI ID:22581659

Ciomperlik, Jessica J. ^[1]; Basta, Holly A. ^[2]

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1. Institute for Molecular Virology and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706 (United States)
2. Department of Biology, Rocky Mountain College, Billings, MT (United States)

Cardiovirus Leader proteins (L{sub X}) inhibit cellular nucleocytoplasmic trafficking by directing host kinases to phosphorylate Phe/Gly-containing nuclear pore proteins (Nups). Resolution of the Mengovirus L{sub M} structure bound to Ran GTPase, suggested this complex would further recruit specific exportins (karyopherins), which in turn mediate kinase selection. Pull-down experiments and recombinant complex reconstitution now confirm that Crm1 and CAS exportins form stable dimeric complexes with encephalomyocarditis virus L{sub E}, and also larger complexes with L{sub E}:Ran. shRNA knockdown studies support this idea. Similar activities could be demonstrated for recombinant L{sub S} and L{sub T} from Theiloviruses. When mutations were introduced to alter the L{sub E} zinc finger domain, acidic domain, or dual phosphorylation sites, there was reduced exportin selection. These regions are not involved in Ran interactions, so the Ran and Crm1 binding sites on L{sub E} must be non-overlapping. The involvement of exportins in this mechanism is important to viral replication and the observation of trafficking inhibition by L{sub E}.

• OSTI ID: 22581659
• Journal Information: Virology, Journal Name: Virology Vol. 487; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
INHIBITION
MUTATIONS
PH VALUE
PHOSPHORYLATION
PHOSPHOTRANSFERASES
SPATIAL RESOLUTION
VIRUSES
ZINC