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5crv

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Revision as of 10:21, 1 April 2020

Crystal structure of the Bro domain of HD-PTP in a complex with the core region of STAM2

Structural highlights

5crv is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5cru
Gene:	PTPN23, KIAA1471 (HUMAN)
Activity:	Protein-tyrosine-phosphatase, with EC number 3.1.3.48
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [STAM2_HUMAN] Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity).

Publication Abstract from PubMed

EGFR is a key player in cell proliferation and survival signaling, and its sorting into MVBs for eventual lysosomal degradation is controlled by the coordination of multiple ESCRT complexes on the endosomal membrane. HD-PTP is a cytosolic protein tyrosine phosphatase, and is associated with EGFR trafficking by interacting with the ESCRT-0 protein STAM2 and the ESCRT-III protein CHMP4B via its N-terminal Bro1 domain. Intriguingly, the homologous domain of two other human Bro1 domain-containing proteins, Alix and Brox, binds CHMP4B but not STAM2, despite their high structural similarity. To elucidate this binding specificity, we determined the complex structure of the HD-PTP Bro1 domain bound to the STAM2 core region. STAM2 binds to the hydrophobic concave pocket of the HD-PTP Bro1 domain, as CHMP4B does to the pocket of Alix, Brox, or HD-PTP but in the opposite direction. Critically, Thr145 of HD-PTP, corresponding to Lys151 of Alix and Arg145 of Brox, is revealed to be a determinant residue enabling this protein to bind STAM2, as the Alix- or Brox-mimicking mutations of this residue blocks the intermolecular interaction. This work therefore provides the structural basis for how HD-PTP recognizes the ESCRT-0 component to control EGFR sorting.

Structural Study of the HD-PTP Bro1 Domain in a Complex with the Core Region of STAM2, a Subunit of ESCRT-0.,Lee J, Oh KJ, Lee D, Kim BY, Choi JS, Ku B, Kim SJ PLoS One. 2016 Feb 11;11(2):e0149113. doi: 10.1371/journal.pone.0149113., eCollection 2016. PMID:26866605^[4]

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

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
↑ Lee J, Oh KJ, Lee D, Kim BY, Choi JS, Ku B, Kim SJ. Structural Study of the HD-PTP Bro1 Domain in a Complex with the Core Region of STAM2, a Subunit of ESCRT-0. PLoS One. 2016 Feb 11;11(2):e0149113. doi: 10.1371/journal.pone.0149113., eCollection 2016. PMID:26866605 doi:http://dx.doi.org/10.1371/journal.pone.0149113

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5crv"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the Bro domain of HD-PTP in a complex with the core region of STAM2==
-<StructureSection load='5crv' size='340' side='right' caption='[[5crv]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5crv' size='340' side='right'caption='[[5crv]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5crv]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CRV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5crv]] is a 4 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=5CRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CRV FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cru|5cru]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN23, KIAA1471 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
-<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=5crv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5crv OCA], [http://pdbe.org/5crv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5crv RCSB], [http://www.ebi.ac.uk/pdbsum/5crv PDBsum]</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=5crv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5crv OCA], [http://pdbe.org/5crv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5crv RCSB], [http://www.ebi.ac.uk/pdbsum/5crv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5crv ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5crv" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Protein-tyrosine-phosphatase]]
 [[Category: Kim, S J]]

5crv

From Proteopedia

Revision as of 10:21, 1 April 2020

Crystal structure of the Bro domain of HD-PTP in a complex with the core region of STAM2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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