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| | <StructureSection load='6jzd' size='340' side='right'caption='[[6jzd]], [[Resolution|resolution]] 2.48Å' scene=''> | | <StructureSection load='6jzd' size='340' side='right'caption='[[6jzd]], [[Resolution|resolution]] 2.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6jzd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [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=6JZD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JZD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6jzd]] is a 3 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=6JZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JZD FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Vash2, Vashl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), SVBP, CCDC23 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.479Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tubulinyl-Tyr_carboxypeptidase Tubulinyl-Tyr carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.17 3.4.17.17] </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=6jzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jzd OCA], [https://pdbe.org/6jzd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jzd RCSB], [https://www.ebi.ac.uk/pdbsum/6jzd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jzd 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=6jzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jzd OCA], [http://pdbe.org/6jzd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jzd RCSB], [http://www.ebi.ac.uk/pdbsum/6jzd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jzd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VASH2_MOUSE VASH2_MOUSE]] Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146868). Acts as an activator of angiogenesis: expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis (PubMed:19204325).<ref>PMID:19204325</ref> <ref>PMID:29146868</ref> [[http://www.uniprot.org/uniprot/SVBP_HUMAN SVBP_HUMAN]] Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin (PubMed:29146869). Also required to enhance the solubility and secretion of VASH1 and VASH2 (PubMed:20736312, PubMed:27879017).<ref>PMID:20736312</ref> <ref>PMID:27879017</ref> <ref>PMID:29146869</ref> | + | [https://www.uniprot.org/uniprot/VASH2_MOUSE VASH2_MOUSE] Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146868). Acts as an activator of angiogenesis: expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis (PubMed:19204325).<ref>PMID:19204325</ref> <ref>PMID:29146868</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The C-terminus of alpha-tubulin undergoes a detyrosination/tyrosination cycle and dysregulation of this cycle is associated with cancer and other diseases. The molecular mechanisms of tubulin tyrosination are well studied, however it has remained unknown how tyrosine is cleaved from the tubulin tail. Here, we report the crystal structure of the long-sought detyrosination enzyme, the VASH2/SVBP heterodimer at 2.2 A resolution and the structure of the tail/VASH2/SVBP complex at 2.5 A resolution. VASH2 possesses a non-canonical Cys-His-Ser catalytic architecture for tyrosine cleavage. The dynamics of the alpha1- and alpha2- helices of VASH2 are related to the insolubility of VASH2. SVBP plays a chaperone-like role by extensively interacting with VASH2 and stabilizing these dynamic helices. A positively charged groove around the catalytic pocket and the alpha1- and alpha2- helices of VASH2 targets the tubulin tail for detyrosination. We provide insights into the mechanisms underlying the cycle of tubulin tyrosine cleavage and religation.
| + | |
| | | | |
| - | Structural basis of tubulin detyrosination by VASH2/SVBP heterodimer.,Zhou C, Yan L, Zhang WH, Liu Z Nat Commun. 2019 Jul 19;10(1):3212. doi: 10.1038/s41467-019-11277-8. PMID:31324789<ref>PMID:31324789</ref>
| + | ==See Also== |
| - | | + | *[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6jzd" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Tubulinyl-Tyr carboxypeptidase]]
| + | [[Category: Chen Z]] |
| - | [[Category: Chen, Z]] | + | [[Category: Ling Y]] |
| - | [[Category: Ling, Y]] | + | [[Category: Zeyuan G]] |
| - | [[Category: Zeyuan, G]] | + | [[Category: Zhu L]] |
| - | [[Category: Zhu, L]] | + | |
| - | [[Category: Cytosolic protein]]
| + | |
| - | [[Category: Svbp]]
| + | |
| - | [[Category: Tubulin detyrosination]]
| + | |
| - | [[Category: Vash2]]
| + | |
| Structural highlights
Function
VASH2_MOUSE Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146868). Acts as an activator of angiogenesis: expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis (PubMed:19204325).[1] [2]
See Also
References
- ↑ Kimura H, Miyashita H, Suzuki Y, Kobayashi M, Watanabe K, Sonoda H, Ohta H, Fujiwara T, Shimosegawa T, Sato Y. Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis. Blood. 2009 May 7;113(19):4810-8. doi: 10.1182/blood-2008-07-170316. Epub 2009, Feb 9. PMID:19204325 doi:http://dx.doi.org/10.1182/blood-2008-07-170316
- ↑ Aillaud C, Bosc C, Peris L, Bosson A, Heemeryck P, Van Dijk J, Le Friec J, Boulan B, Vossier F, Sanman LE, Syed S, Amara N, Coute Y, Lafanechere L, Denarier E, Delphin C, Pelletier L, Humbert S, Bogyo M, Andrieux A, Rogowski K, Moutin MJ. Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation. Science. 2017 Dec 15;358(6369):1448-1453. doi: 10.1126/science.aao4165. Epub 2017, Nov 16. PMID:29146868 doi:http://dx.doi.org/10.1126/science.aao4165
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