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Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1.
- Source :
-
Structure (London, England : 1993) [Structure] 2016 Dec 06; Vol. 24 (12), pp. 2115-2126. Date of Electronic Publication: 2016 Nov 10. - Publication Year :
- 2016
-
Abstract
- 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.<br /> (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Binding Sites
Crystallography, X-Ray
Endosomal Sorting Complexes Required for Transport metabolism
Humans
Models, Molecular
Protein Binding
Protein Structure, Secondary
Carrier Proteins chemistry
Carrier Proteins metabolism
Protein Tyrosine Phosphatases, Non-Receptor chemistry
Protein Tyrosine Phosphatases, Non-Receptor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-4186
- Volume :
- 24
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Structure (London, England : 1993)
- Publication Type :
- Academic Journal
- Accession number :
- 27839950
- Full Text :
- https://doi.org/10.1016/j.str.2016.10.006