|
|
| Line 1: |
Line 1: |
| | | | |
| | ==C-terminal domain of Vps54 subunit of the GARP complex== | | ==C-terminal domain of Vps54 subunit of the GARP complex== |
| - | <StructureSection load='3n1b' size='340' side='right' caption='[[3n1b]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='3n1b' size='340' side='right'caption='[[3n1b]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3n1b]] is a 2 chain structure with sequence from [http://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=3N1B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N1B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3n1b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N1B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N1B FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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]] 2.398Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2a2f|2a2f]], [[2fji|2fji]], [[3fhn|3fhn]], [[2pfv|2pfv]], [[3hr0|3hr0]], [[3n1e|3n1e]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Vps54 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n1b OCA], [https://pdbe.org/3n1b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n1b RCSB], [https://www.ebi.ac.uk/pdbsum/3n1b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n1b ProSAT]</span></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=3n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n1b OCA], [http://pdbe.org/3n1b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n1b RCSB], [http://www.ebi.ac.uk/pdbsum/3n1b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n1b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/VPS54_MOUSE VPS54_MOUSE]] Note=Defects in Vps54 are the cause of wobbler phenotype (wr). Wr is autosomal recessive and is a spontaneous mutation discovered almost 50 years ago. It causes spinal muscular atrophy and defective spermiogenesis.<ref>PMID:16244655</ref> | + | [https://www.uniprot.org/uniprot/VPS54_MOUSE VPS54_MOUSE] Note=Defects in Vps54 are the cause of wobbler phenotype (wr). Wr is autosomal recessive and is a spontaneous mutation discovered almost 50 years ago. It causes spinal muscular atrophy and defective spermiogenesis.<ref>PMID:16244655</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VPS54_MOUSE VPS54_MOUSE]] May be involved in retrograde transport from early and late endosomes to the late Golgi. The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (By similarity). | + | [https://www.uniprot.org/uniprot/VPS54_MOUSE VPS54_MOUSE] May be involved in retrograde transport from early and late endosomes to the late Golgi. The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n1/3n1b_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n1/3n1b_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| Line 32: |
Line 31: |
| | </div> | | </div> |
| | <div class="pdbe-citations 3n1b" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3n1b" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Vacuolar protein sorting-associated protein 3D structures|Vacuolar protein sorting-associated protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Abascal-Palacios, G]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bonifacino, J S]] | + | [[Category: Abascal-Palacios G]] |
| - | [[Category: Hierro, A]] | + | [[Category: Bonifacino JS]] |
| - | [[Category: Kajava, A]] | + | [[Category: Hierro A]] |
| - | [[Category: Perez-Victoria, F J]] | + | [[Category: Kajava A]] |
| - | [[Category: Pioro, E P]] | + | [[Category: Perez-Victoria FJ]] |
| - | [[Category: Tascon, I]] | + | [[Category: Pioro EP]] |
| - | [[Category: Garp]]
| + | [[Category: Tascon I]] |
| - | [[Category: Golgi apparatus]]
| + | |
| - | [[Category: Spinal muscular atrophy]]
| + | |
| - | [[Category: Tethering complex]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Vesicle trafficking]]
| + | |
| Structural highlights
Disease
VPS54_MOUSE Note=Defects in Vps54 are the cause of wobbler phenotype (wr). Wr is autosomal recessive and is a spontaneous mutation discovered almost 50 years ago. It causes spinal muscular atrophy and defective spermiogenesis.[1]
Function
VPS54_MOUSE May be involved in retrograde transport from early and late endosomes to the late Golgi. The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The multisubunit Golgi-associated retrograde protein (GARP) complex is required for tethering and fusion of endosome-derived transport vesicles to the trans-Golgi network. Mutation of leucine-967 to glutamine in the Vps54 subunit of GARP is responsible for spinal muscular atrophy in the wobbler mouse, an animal model of amyotrophic lateral sclerosis. The crystal structure at 1.7 A resolution of the mouse Vps54 C-terminal fragment harboring leucine-967, in conjunction with comparative sequence analysis, reveals that Vps54 has a continuous alpha-helical bundle organization similar to that of other multisubunit tethering complexes. The structure shows that leucine-967 is buried within the alpha-helical bundle through predominantly hydrophobic interactions that are critical for domain stability and folding in vitro. Mutation of this residue to glutamine does not prevent integration of Vps54 into the GARP complex but greatly reduces the half-life and levels of the protein in vivo. Severely reduced levels of mutant Vps54 and, consequently, of the whole GARP complex underlie the phenotype of the wobbler mouse.
Structural basis for the wobbler mouse neurodegenerative disorder caused by mutation in the Vps54 subunit of the GARP complex.,Perez-Victoria FJ, Abascal-Palacios G, Tascon I, Kajava A, Magadan JG, Pioro EP, Bonifacino JS, Hierro A Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12860-5. Epub 2010 Jul 6. PMID:20615984[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schmitt-John T, Drepper C, Mussmann A, Hahn P, Kuhlmann M, Thiel C, Hafner M, Lengeling A, Heimann P, Jones JM, Meisler MH, Jockusch H. Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse. Nat Genet. 2005 Nov;37(11):1213-5. Epub 2005 Oct 23. PMID:16244655 doi:10.1038/ng1661
- ↑ Perez-Victoria FJ, Abascal-Palacios G, Tascon I, Kajava A, Magadan JG, Pioro EP, Bonifacino JS, Hierro A. Structural basis for the wobbler mouse neurodegenerative disorder caused by mutation in the Vps54 subunit of the GARP complex. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12860-5. Epub 2010 Jul 6. PMID:20615984
|
