6iwa

From Proteopedia

(Difference between revisions)

Revision as of 10:21, 2 October 2019

Crystal structure of Importin-alpha and phosphoserine GM130

Structural highlights

6iwa is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] [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

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Puthenveedu MA, Bachert C, Puri S, Lanni F, Linstedt AD. GM130 and GRASP65-dependent lateral cisternal fusion allows uniform Golgi-enzyme distribution. Nat Cell Biol. 2006 Mar;8(3):238-48. Epub 2006 Feb 19. PMID:16489344 doi:http://dx.doi.org/10.1038/ncb1366
↑ Marra P, Salvatore L, Mironov A Jr, Di Campli A, Di Tullio G, Trucco A, Beznoussenko G, Mironov A, De Matteis MA. The biogenesis of the Golgi ribbon: the roles of membrane input from the ER and of GM130. Mol Biol Cell. 2007 May;18(5):1595-608. Epub 2007 Feb 21. PMID:17314401 doi:http://dx.doi.org/10.1091/mbc.E06-10-0886
↑ Kodani A, Sutterlin C. The Golgi protein GM130 regulates centrosome morphology and function. Mol Biol Cell. 2008 Feb;19(2):745-53. Epub 2007 Nov 28. PMID:18045989 doi:http://dx.doi.org/10.1091/mbc.E07-08-0847
↑ Kodani A, Kristensen I, Huang L, Sutterlin C. GM130-dependent control of Cdc42 activity at the Golgi regulates centrosome organization. Mol Biol Cell. 2009 Feb;20(4):1192-200. doi: 10.1091/mbc.E08-08-0834. Epub 2008, Dec 24. PMID:19109421 doi:http://dx.doi.org/10.1091/mbc.E08-08-0834
↑ Rivero S, Cardenas J, Bornens M, Rios RM. Microtubule nucleation at the cis-side of the Golgi apparatus requires AKAP450 and GM130. EMBO J. 2009 Apr 22;28(8):1016-28. doi: 10.1038/emboj.2009.47. Epub 2009 Feb 26. PMID:19242490 doi:http://dx.doi.org/10.1038/emboj.2009.47
↑ Wei JH, Zhang ZC, Wynn RM, Seemann J. GM130 Regulates Golgi-Derived Spindle Assembly by Activating TPX2 and Capturing Microtubules. Cell. 2015 Jul 16;162(2):287-99. doi: 10.1016/j.cell.2015.06.014. Epub 2015 Jul, 9. PMID:26165940 doi:http://dx.doi.org/10.1016/j.cell.2015.06.014
↑ Chang CC, Chen CJ, Grauffel C, Pien YC, Lim C, Tsai SY, Hsia KC. Ran pathway-independent regulation of mitotic Golgi disassembly by Importin-alpha. Nat Commun. 2019 Sep 20;10(1):4307. doi: 10.1038/s41467-019-12207-4. PMID:31541088 doi:http://dx.doi.org/10.1038/s41467-019-12207-4

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6iwa"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6iwa is ON HOLD
+==Crystal structure of Importin-alpha and phosphoserine GM130==
+<StructureSection load='6iwa' size='340' side='right'caption='[[6iwa]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6iwa]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IWA FirstGlance]. <br>
+</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6iwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iwa OCA], [http://pdbe.org/6iwa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6iwa RCSB], [http://www.ebi.ac.uk/pdbsum/6iwa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6iwa ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://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>  [[http://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;">
+== 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).
-Authors: Chang, C.-C., Chen, C.-J., Pien, Y.-C., Tsai, S.-Y., Hsia, K.-C.
+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>
-Description: Crystal structure of Importin-alpha and phosphoserine GM130
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chang, C.-C]]
+<div class="pdbe-citations 6iwa" style="background-color:#fffaf0;"></div>
-[[Category: Chen, C.-J]]
+== References ==
-[[Category: Tsai, S.-Y]]
+<references/>
-[[Category: Hsia, K.-C]]
+__TOC__
-[[Category: Pien, Y.-C]]
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Chang, C C]]
+[[Category: Chen, C J]]
+[[Category: Hsia, K C]]
+[[Category: Pien, Y C]]
+[[Category: Tsai, S Y]]
+[[Category: Gm130]]
+[[Category: Importin alpha]]
+[[Category: Protein binding]]

6iwa

From Proteopedia

Revision as of 10:21, 2 October 2019

Crystal structure of Importin-alpha and phosphoserine GM130

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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