5lm2
From Proteopedia
Crystal Structure of HD-PTP phosphatase
Structural highlights
FunctionPTN23_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 PubMedEndosomal 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. See AlsoReferences
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