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| | ==Crystal structure of the GRASP55 GRASP Domain with a phosphomimetic mutation (S189D)== | | ==Crystal structure of the GRASP55 GRASP Domain with a phosphomimetic mutation (S189D)== |
| - | <StructureSection load='4edj' size='340' side='right' caption='[[4edj]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4edj' size='340' side='right'caption='[[4edj]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4edj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4edj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EDJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rle|3rle]]</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=4edj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edj OCA], [https://pdbe.org/4edj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4edj RCSB], [https://www.ebi.ac.uk/pdbsum/4edj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4edj ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GORASP2, GOLPH6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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=4edj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edj OCA], [http://pdbe.org/4edj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4edj RCSB], [http://www.ebi.ac.uk/pdbsum/4edj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4edj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GORS2_HUMAN GORS2_HUMAN]] Plays a role in the assembly and membrane stacking of the Golgi cisternae, and in the process by which Golgi stacks reform after mitotic breakdown. May regulate the intracellular transport and presentation of a defined set of transmembrane proteins, such as transmembrane TGFA.<ref>PMID:10487747</ref> <ref>PMID:21515684</ref> | + | [[https://www.uniprot.org/uniprot/GORS2_HUMAN GORS2_HUMAN]] Plays a role in the assembly and membrane stacking of the Golgi cisternae, and in the process by which Golgi stacks reform after mitotic breakdown. May regulate the intracellular transport and presentation of a defined set of transmembrane proteins, such as transmembrane TGFA.<ref>PMID:10487747</ref> <ref>PMID:21515684</ref> |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bachert, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Linstedt, A D]] | + | [[Category: Bachert C]] |
| - | [[Category: Macbeth, M R]] | + | [[Category: Linstedt AD]] |
| - | [[Category: Truschel, S T]] | + | [[Category: Macbeth MR]] |
| - | [[Category: Zhang, M]] | + | [[Category: Truschel ST]] |
| - | [[Category: Golgi tethering]]
| + | [[Category: Zhang M]] |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Pdz domain]]
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| Structural highlights
Function
[GORS2_HUMAN] Plays a role in the assembly and membrane stacking of the Golgi cisternae, and in the process by which Golgi stacks reform after mitotic breakdown. May regulate the intracellular transport and presentation of a defined set of transmembrane proteins, such as transmembrane TGFA.[1] [2]
Publication Abstract from PubMed
Mitotic phosphorylation of the conserved GRASP domain of GRASP65 disrupts its self-association leading to a loss of Golgi membrane tethering, cisternal unlinking and Golgi breakdown. Recently the structural basis of the GRASP self-interaction was determined, yet the mechanism by which phosphorylation disrupts this activity is unknown. Here we present the crystal structure of a GRASP phosphomimic containing an aspartic acid substitution for a serine residue (Ser189) that in GRASP65 is phosphorylated by Polo-like kinase I causing a block in membrane tethering and Golgi ribbon formation. The structure revealed a conformational change in the GRASP internal ligand that prevented its insertion into the PDZ binding pocket and gel filtration assays showed that this phosphomimetic mutant exhibited a significant reduction in dimer formation. Interestingly, the structure also revealed an apparent propagation of conformational change from the site of phosphorylation to the shifted ligand and alanine substitution of two residues (Glu145 and Ser146) at penultimate positions in this chain rescued dimer formation by the phosphomimic. These data reveal the structural basis of the phosphoinhibition of GRASP-mediated membrane tethering and provide a mechanism for its allosteric regulation.
Allosteric regulation of GRASP-dependent Golgi membrane tethering by mitotic phosphorylation.,Truschel ST, Zhang M, Bachert C, Macbeth MR, Linstedt AD J Biol Chem. 2012 Apr 20. PMID:22523075[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shorter J, Watson R, Giannakou ME, Clarke M, Warren G, Barr FA. GRASP55, a second mammalian GRASP protein involved in the stacking of Golgi cisternae in a cell-free system. EMBO J. 1999 Sep 15;18(18):4949-60. PMID:10487747 doi:http://dx.doi.org/10.1093/emboj/18.18.4949
- ↑ Truschel ST, Sengupta D, Foote A, Heroux A, Macbeth MR, Linstedt AD. Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis. J Biol Chem. 2011 Jun 10;286(23):20125-9. Epub 2011 Apr 22. PMID:21515684 doi:10.1074/jbc.C111.245324
- ↑ Truschel ST, Zhang M, Bachert C, Macbeth MR, Linstedt AD. Allosteric regulation of GRASP-dependent Golgi membrane tethering by mitotic phosphorylation. J Biol Chem. 2012 Apr 20. PMID:22523075 doi:10.1074/jbc.M111.326256
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