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| | <StructureSection load='3uky' size='340' side='right'caption='[[3uky]], [[Resolution|resolution]] 2.35Å' scene=''> | | <StructureSection load='3uky' size='340' side='right'caption='[[3uky]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3uky]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UKY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3uky]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UKY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ial|1ial]], [[3fex|3fex]], [[3fey|3fey]], [[3ukw|3ukw]], [[3ukx|3ukx]], [[3ukz|3ukz]], [[3ul0|3ul0]], [[3ul1|3ul1]]</div></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]] 2.35Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kpna2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), CBP80 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=3uky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uky OCA], [https://pdbe.org/3uky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uky RCSB], [https://www.ebi.ac.uk/pdbsum/3uky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uky 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=3uky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uky OCA], [https://pdbe.org/3uky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uky RCSB], [https://www.ebi.ac.uk/pdbsum/3uky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uky ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/IMA2_MOUSE IMA2_MOUSE]] 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. [[https://www.uniprot.org/uniprot/NCBP1_YEAST NCBP1_YEAST]] Component of the CBC complex, which binds co-transcriptionally to the 5'-cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs. The CBC complex is required for efficient pre-mRNA splicing through efficient commitment complex and spliceosome formation. Together with NPL3, the CBC complex is required for export of mRNAs out of the nucleus. The CBC complex is also involved in nuclear mRNA degradation, probably by directing the mRNAs to the sites of degradation. Affects replication of the positive-strand RNA virus BMV.<ref>PMID:10490594</ref> <ref>PMID:10733586</ref> <ref>PMID:10823828</ref> <ref>PMID:12756324</ref> <ref>PMID:12897126</ref> <ref>PMID:14671320</ref> <ref>PMID:1512188</ref> <ref>PMID:15753296</ref> <ref>PMID:16166263</ref> <ref>PMID:8811086</ref> <ref>PMID:8846890</ref> <ref>PMID:8858145</ref> <ref>PMID:9499403</ref>
| + | [https://www.uniprot.org/uniprot/IMA1_MOUSE IMA1_MOUSE] 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Forwood, J K]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Kobe, B]] | + | [[Category: Forwood JK]] |
| - | [[Category: Lonhienne, T G]] | + | [[Category: Kobe B]] |
| - | [[Category: Marfori, M]] | + | [[Category: Lonhienne TG]] |
| - | [[Category: Arm repeat]] | + | [[Category: Marfori M]] |
| - | [[Category: Armadillo repeat]]
| + | |
| - | [[Category: Importin beta binding]]
| + | |
| - | [[Category: Nuclear localisation signal binding]]
| + | |
| - | [[Category: Nuclear transport]]
| + | |
| - | [[Category: Protein transport-protein binding complex]]
| + | |
| Structural highlights
Function
IMA1_MOUSE 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.
Publication Abstract from PubMed
Classical nuclear localization signals (cNLSs), comprising one (monopartite cNLSs) or two clusters of basic residues connected by a 10-12 residue linker (bipartite cNLSs), are recognized by the nuclear import factor importin-alpha. The cNLSs bind along a concave groove on importin-alpha; however, specificity determinants of cNLSs remain poorly understood. We present a structural and interaction analysis study of importin-alpha binding to both designed and naturally occurring high-affinity cNLS-like sequences; the peptide inhibitors Bimax1 and Bimax2, and cNLS peptides of cap-binding protein 80. Our data suggest that cNLSs and cNLS-like sequences can achieve high affinity through maximizing interactions at the importin-alpha minor site, and by taking advantage of multiple linker region interactions. Our study defines an extended set of binding cavities on the importin-alpha surface, and also expands on recent observations that longer linker sequences are allowed, and that long-range electrostatic complementarity can contribute to cNLS-binding affinity. Altogether, our study explains the molecular and structural basis of the results of a number of recent studies, including systematic mutagenesis and peptide library approaches, and provides an improved level of understanding on the specificity determinants of a cNLS. Our results have implications for identifying cNLSs in novel proteins.
Structural Basis of High-Affinity Nuclear Localization Signal Interactions with Importin-alpha,Marfori M, Lonhienne TG, Forwood JK, Kobe B Traffic. 2012 Jan 16. doi: 10.1111/j.1600-0854.2012.01329.x. PMID:22248489[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Marfori M, Lonhienne TG, Forwood JK, Kobe B. Structural Basis of High-Affinity Nuclear Localization Signal Interactions with Importin-alpha Traffic. 2012 Jan 16. doi: 10.1111/j.1600-0854.2012.01329.x. PMID:22248489 doi:10.1111/j.1600-0854.2012.01329.x
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