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| | ==Importin alpha 7 delta IBB in complex with Influenza PB2 Nuclear Localization Domain== | | ==Importin alpha 7 delta IBB in complex with Influenza PB2 Nuclear Localization Domain== |
| - | <StructureSection load='4uad' size='340' side='right' caption='[[4uad]], [[Resolution|resolution]] 2.42Å' scene=''> | + | <StructureSection load='4uad' size='340' side='right'caption='[[4uad]], [[Resolution|resolution]] 2.42Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uad]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UAD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UAD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uad]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Victoria/3/1975(H3N2)) Influenza A virus (A/Victoria/3/1975(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UAD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UAD FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uae|4uae]], [[4uaf|4uaf]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.42Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uad OCA], [http://pdbe.org/4uad PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uad RCSB], [http://www.ebi.ac.uk/pdbsum/4uad PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uad ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4uad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uad OCA], [https://pdbe.org/4uad PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uad RCSB], [https://www.ebi.ac.uk/pdbsum/4uad PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uad ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IMA7_HUMAN IMA7_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.<ref>PMID:10523667</ref> [[http://www.uniprot.org/uniprot/PB2_I75A3 PB2_I75A3]] Involved in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNA are used to generate primers for viral transcription. Binds the cap of the target pre-RNA which is subsequently cleaved by PB1. May play a role in genome replication (By similarity). | + | [https://www.uniprot.org/uniprot/IMA7_HUMAN IMA7_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.<ref>PMID:10523667</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Importin|Importin]] | + | *[[Importin 3D structures|Importin 3D structures]] |
| - | *[[RNA polymerase|RNA polymerase]] | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cingolani, G]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Pumroy, R A]] | + | [[Category: Large Structures]] |
| - | [[Category: Importin karyopherin complex nl]] | + | [[Category: Cingolani G]] |
| - | [[Category: Protein transport]] | + | [[Category: Pumroy RA]] |
| Structural highlights
Function
IMA7_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 PubMed
Influenza 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 Also
References
- ↑ Kohler M, Speck C, Christiansen M, Bischoff FR, Prehn S, Haller H, Gorlich D, Hartmann E. Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import. Mol Cell Biol. 1999 Nov;19(11):7782-91. PMID:10523667
- ↑ Pumroy RA, Ke S, Hart DJ, Zachariae U, Cingolani G. Molecular Determinants for Nuclear Import of Influenza A PB2 by Importin alpha Isoforms 3 and 7. Structure. 2015 Feb 3;23(2):374-84. doi: 10.1016/j.str.2014.11.015. Epub 2015 Jan, 15. PMID:25599645 doi:http://dx.doi.org/10.1016/j.str.2014.11.015
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