6iwa
From Proteopedia
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- | '''Unreleased structure''' | ||
- | + | ==Crystal structure of Importin-alpha and phosphoserine GM130== | |
+ | <StructureSection load='6iwa' size='340' side='right'caption='[[6iwa]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[6iwa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IWA FirstGlance]. <br> | ||
+ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
+ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=6iwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iwa OCA], [https://pdbe.org/6iwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iwa RCSB], [https://www.ebi.ac.uk/pdbsum/6iwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iwa ProSAT]</span></td></tr> | ||
+ | </table> | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/GOGA2_HUMAN GOGA2_HUMAN] Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane. Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis (By similarity). Also plays a key role in spindle pole assembly and centrosome organization (PubMed:26165940). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (PubMed:19242490, PubMed:26165940). Regulates the meiotic spindle pole assembly, probably via the same mechanism (By similarity). Also regulates the centrosome organization (PubMed:18045989, PubMed:19109421). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (PubMed:16489344, PubMed:17314401).[UniProtKB:Q62839][UniProtKB:Q921M4]<ref>PMID:16489344</ref> <ref>PMID:17314401</ref> <ref>PMID:18045989</ref> <ref>PMID:19109421</ref> <ref>PMID:19242490</ref> <ref>PMID:26165940</ref> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | To facilitate proper mitotic cell partitioning, the Golgi disassembles by suppressing vesicle fusion. However, the underlying mechanism has not been characterized previously. Here, we report a Ran pathway-independent attenuation mechanism that allows Importin-alpha (a nuclear transport factor) to suppress the vesicle fusion mediated by p115 (a vesicular tethering factor) and is required for mitotic Golgi disassembly. We demonstrate that Importin-alpha directly competes with p115 for interaction with the Golgi protein GM130. This interaction, promoted by a phosphate moiety on GM130, is independent of Importin-beta and Ran. A GM130 K34A mutant, in which the Importin-alpha-GM130 interaction is specifically disrupted, exhibited abundant Golgi puncta during metaphase. Importantly, a mutant showing enhanced p115-GM130 interaction presented proliferative defects and G2/M arrest, demonstrating that Importin-alpha-GM130 binding modulates the Golgi disassembly that governs mitotic progression. Our findings illuminate that the Ran and kinase-phosphatase pathways regulate multiple aspects of mitosis coordinated by Importin-alpha (e.g. spindle assembly, Golgi disassembly). | ||
- | + | Ran pathway-independent regulation of mitotic Golgi disassembly by Importin-alpha.,Chang CC, Chen CJ, Grauffel C, Pien YC, Lim C, Tsai SY, Hsia KC Nat Commun. 2019 Sep 20;10(1):4307. doi: 10.1038/s41467-019-12207-4. PMID:31541088<ref>PMID:31541088</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | [[Category: | + | </div> |
- | [[Category: Chang | + | <div class="pdbe-citations 6iwa" style="background-color:#fffaf0;"></div> |
- | [[Category: Chen | + | |
- | [[Category: | + | ==See Also== |
- | [[Category: | + | *[[Importin 3D structures|Importin 3D structures]] |
- | [[Category: | + | == References == |
+ | <references/> | ||
+ | __TOC__ | ||
+ | </StructureSection> | ||
+ | [[Category: Homo sapiens]] | ||
+ | [[Category: Large Structures]] | ||
+ | [[Category: Mus musculus]] | ||
+ | [[Category: Chang C-C]] | ||
+ | [[Category: Chen C-J]] | ||
+ | [[Category: Hsia K-C]] | ||
+ | [[Category: Pien Y-C]] | ||
+ | [[Category: Tsai S-Y]] |
Current revision
Crystal structure of Importin-alpha and phosphoserine GM130
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Categories: Homo sapiens | Large Structures | Mus musculus | Chang C-C | Chen C-J | Hsia K-C | Pien Y-C | Tsai S-Y