Unknown

Dataset Information

0

Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1.


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.

SUBMITTER: Gahloth D 

PROVIDER: S-EPMC5145805 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1.

Gahloth Deepankar D   Levy Colin C   Heaven Graham G   Stefani Flavia F   Wunderley Lydia L   Mould Paul P   Cliff Matthew J MJ   Bella Jordi J   Fielding Alistair J AJ   Woodman Philip P   Tabernero Lydia L  

Structure (London, England : 1993) 20161110 12


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  ...[more]

Similar Datasets

| S-EPMC5501724 | biostudies-literature
| S-EPMC4007767 | biostudies-literature
| S-EPMC4751086 | biostudies-literature
| S-EPMC8567383 | biostudies-literature
| S-EPMC5567221 | biostudies-literature
| S-EPMC5773591 | biostudies-literature
| S-EPMC3527972 | biostudies-literature
| S-EPMC4294665 | biostudies-literature
| S-EPMC2712734 | biostudies-literature
| S-EPMC9410543 | biostudies-literature