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Gahloth, D, Levy, C, Heaven, G, Stefani, F, Wunderley, L, Mould, P, Cliff, M, Bella, J, Fielding, AJ, Woodman, P and Tabernero, L (2016) Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1. Structure, 24 (12). pp. 2115-2126. ISSN 0969-2126
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Molecular architecture of the tyrosine phosphatase HD-PTP and the structural basis for its specific interaction with UBAP1 .pdf - Accepted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (792kB) | Preview |
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.
| Item Type: | Article |
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| Uncontrolled Keywords: | 06 Biological Sciences, 08 Information And Computing Sciences, 03 Chemical Sciences |
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Elsevier |
| Date Deposited: | 14 Feb 2018 09:24 |
| Last Modified: | 04 Sep 2021 03:14 |
| DOI or ID number: | 10.1016/j.str.2016.10.006 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/8019 |
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