5lm2

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Crystal Structure of HD-PTP phosphatase

Structural highlights

5lm2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.54Å
Ligands:MSE
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]

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.

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[4]

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

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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ Gahloth D, Levy C, Heaven G, Stefani F, Wunderley L, Mould P, Cliff MJ, Bella J, Fielding AJ, Woodman P, Tabernero L. Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1. Structure. 2016 Dec 6;24(12):2115-2126. doi: 10.1016/j.str.2016.10.006. Epub 2016, Nov 10. PMID:27839950 doi:http://dx.doi.org/10.1016/j.str.2016.10.006

Contents


PDB ID 5lm2

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