Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1.
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.
Mesh Terms:
Binding Sites, Carrier Proteins, Crystallography, X-Ray, Endosomal Sorting Complexes Required for Transport, Humans, Models, Molecular, Protein Binding, Protein Structure, Secondary, Protein Tyrosine Phosphatases, Non-Receptor
Binding Sites, Carrier Proteins, Crystallography, X-Ray, Endosomal Sorting Complexes Required for Transport, Humans, Models, Molecular, Protein Binding, Protein Structure, Secondary, Protein Tyrosine Phosphatases, Non-Receptor
Structure
Date: Dec. 06, 2016
PubMed ID: 27839950
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