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| | ==Crystal Structure of HD-PTP phosphatase in complex with UBAP1== | | ==Crystal Structure of HD-PTP phosphatase in complex with UBAP1== |
| - | <StructureSection load='5lm1' size='340' side='right' caption='[[5lm1]], [[Resolution|resolution]] 2.55Å' scene=''> | + | <StructureSection load='5lm1' size='340' side='right'caption='[[5lm1]], [[Resolution|resolution]] 2.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lm1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LM1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LM1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lm1]] 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=5LM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LM1 FirstGlance]. <br> |
| - | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></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]] 2.55Å</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=5lm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lm1 OCA], [http://pdbe.org/5lm1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lm1 RCSB], [http://www.ebi.ac.uk/pdbsum/5lm1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lm1 ProSAT]</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=5lm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lm1 OCA], [https://pdbe.org/5lm1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lm1 RCSB], [https://www.ebi.ac.uk/pdbsum/5lm1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lm1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTN23_HUMAN PTN23_HUMAN]] Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis.<ref>PMID:18434552</ref> <ref>PMID:20393563</ref> <ref>PMID:21757351</ref> | + | [https://www.uniprot.org/uniprot/PTN23_HUMAN PTN23_HUMAN] Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis.<ref>PMID:18434552</ref> <ref>PMID:20393563</ref> <ref>PMID:21757351</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Endosomal sorting complexes required for transport (ESCRTs) are essential for ubiquitin-dependent degradation of mitogenic receptors, a process often compromised in cancer pathologies. Sorting of ubiquinated receptors via ESCRTs is controlled by the tumor suppressor phosphatase HD-PTP. The specific interaction between HD-PTP and the ESCRT-I subunit UBAP1 is critical for degradation of growth factor receptors and integrins. Here, we present the structural characterization by X-ray crystallography and double electron-electron resonance spectroscopy of the coiled-coil domain of HD-PTP and its complex with UBAP1. The coiled-coil domain adopts an unexpected open and rigid conformation that contrasts with the closed and flexible coiled-coil domain of the related ESCRT regulator Alix. The HD-PTP:UBAP1 structure identifies the molecular determinants of the interaction and provides a molecular basis for the specific functional cooperation between HD-PTP and UBAP1. Our findings provide insights into the molecular mechanisms of regulation of ESCRT pathways that could be relevant to anticancer therapies.
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| - | Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1.,Gahloth D, Levy C, Heaven G, Stefani F, Wunderley L, Mould P, Cliff MJ, Bella J, Fielding AJ, Woodman P, Tabernero L Structure. 2016 Dec 6;24(12):2115-2126. doi: 10.1016/j.str.2016.10.006. Epub 2016, Nov 10. PMID:27839950<ref>PMID:27839950</ref>
| + | ==See Also== |
| - | | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5lm1" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Levy, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Coiled coil]] | + | [[Category: Levy C]] |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
PTN23_HUMAN Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis.[1] [2] [3]
See Also
References
- ↑ Doyotte A, Mironov A, McKenzie E, Woodman P. The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6308-13. doi:, 10.1073/pnas.0707601105. Epub 2008 Apr 23. PMID:18434552 doi:http://dx.doi.org/10.1073/pnas.0707601105
- ↑ Kim J, Lee JE, Heynen-Genel S, Suyama E, Ono K, Lee K, Ideker T, Aza-Blanc P, Gleeson JG. Functional genomic screen for modulators of ciliogenesis and cilium length. Nature. 2010 Apr 15;464(7291):1048-51. doi: 10.1038/nature08895. PMID:20393563 doi:10.1038/nature08895
- ↑ Stefani F, Zhang L, Taylor S, Donovan J, Rollinson S, Doyotte A, Brownhill K, Bennion J, Pickering-Brown S, Woodman P. UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting. Curr Biol. 2011 Jul 26;21(14):1245-50. doi: 10.1016/j.cub.2011.06.028. Epub 2011 , Jul 14. PMID:21757351 doi:http://dx.doi.org/10.1016/j.cub.2011.06.028
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