5mk0
From Proteopedia
(Difference between revisions)
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== 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> [[http://www.uniprot.org/uniprot/ZFY16_HUMAN ZFY16_HUMAN]] May be involved in regulating membrane trafficking in the endosomal pathway. Overexpression induces endosome aggregation. Required to target TOM1 to endosomes.<ref>PMID:11546807</ref> <ref>PMID:14613930</ref> | [[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> [[http://www.uniprot.org/uniprot/ZFY16_HUMAN ZFY16_HUMAN]] May be involved in regulating membrane trafficking in the endosomal pathway. Overexpression induces endosome aggregation. Required to target TOM1 to endosomes.<ref>PMID:11546807</ref> <ref>PMID:14613930</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | SARA and endofin are endosomal adaptor proteins that drive Smad phosphorylation by ligand-activated transforming growth factor beta/bone morphogenetic protein (TGFbeta/BMP) receptors. We show in this study that SARA and endofin also recruit the tumor supressor HD-PTP, a master regulator of endosomal sorting and ESCRT-dependent receptor downregulation. High-affinity interactions occur between the SARA/endofin N termini, and the conserved hydrophobic region in the HD-PTP Bro1 domain that binds CHMP4/ESCRT-III. CHMP4 engagement is a universal feature of Bro1 proteins, but SARA/endofin binding is specific to HD-PTP. Crystallographic structures of HD-PTPBro1 in complex with SARA, endofin, and three CHMP4 isoforms revealed that all ligands bind similarly to the conserved site but, critically, only SARA/endofin interact at a neighboring pocket unique to HD-PTP. The structures, together with mutagenesis and binding analysis, explain the high affinity and specific binding of SARA/endofin, and why they compete so effectively with CHMP4. Our data invoke models for how endocytic regulation of TGFbeta/BMP signaling is controlled. | ||
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| + | Structural Basis for Specific Interaction of TGFbeta Signaling Regulators SARA/Endofin with HD-PTP.,Gahloth D, Levy C, Walker L, Wunderley L, Mould AP, Taylor S, Woodman P, Tabernero L Structure. 2017 Jul 5;25(7):1011-1024.e4. doi: 10.1016/j.str.2017.05.005. Epub, 2017 Jun 8. PMID:28602823<ref>PMID:28602823</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5mk0" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 07:41, 6 December 2017
Crystal structure of the His Domain Protein Tyrosine Phosphatase (HD-PTP/PTPN23) Bro1 domain (Endofin peptide complex)
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