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Importin alpha 7 delta IBB in complex with Influenza PB2 Nuclear Localization Domain
Structural highlights
FunctionIMA7_HUMAN Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.[1] Publication Abstract from PubMedInfluenza A virus polymerase subunit PB2 is a major virulence determinant implicated in pathogenicity and host adaptation. During cross-species virus transfer from avian to mammalian cells, PB2 switches specificity from importin alpha3 to alpha7. This specificity is not recapitulated in vitro, where PB2 binds all importin alpha isoforms with comparably high affinity. In this study, we investigated the structure, conformational dynamics, and autoinhibition of importin alpha isoforms 1, 3, and 7 in complex with PB2. Our data suggest that association of PB2 with alpha3 and alpha7 is favored by reduced autoinhibition of these isoforms and by the unique structure of the nuclear localization signal (NLS) domain of PB2. We propose that by recruiting importin alpha3 or alpha7 in the absence of importin beta, PB2 reduces the complexity of adaptor-mediated import to a pseudo-bimolecular reaction, thereby acquiring a kinetic advantage over classical NLS cargos, which form an import complex only when importin alpha and beta are simultaneously available. Molecular Determinants for Nuclear Import of Influenza A PB2 by Importin alpha Isoforms 3 and 7.,Pumroy RA, Ke S, Hart DJ, Zachariae U, Cingolani G Structure. 2015 Feb 3;23(2):374-84. doi: 10.1016/j.str.2014.11.015. Epub 2015 Jan, 15. PMID:25599645[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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