5LM1

Crystal Structure of HD-PTP phosphatase in complex with UBAP1

Summary for 5LM1

• Entry DOI: 10.2210/pdb5lm1/pdb
• Descriptor: Tyrosine-protein phosphatase non-receptor type 23, UBAP-1 (3 entities in total)
• Functional Keywords: coiled coil, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: Q9H3S7
• Total number of polymer chains: 2
• Total formula weight: 42389.98

Authors

Levy, C. (deposition date: 2016-07-28, release date: 2016-11-30, Last modification date: 2024-05-01)

Primary citation

Gahloth, D.,Levy, C.,Heaven, G.,Stefani, F.,Wunderley, L.,Mould, P.,Cliff, M.J.,Bella, J.,Fielding, A.J.,Woodman, P.,Tabernero, L.
Structural Basis for Selective Interaction between the ESCRT Regulator HD-PTP and UBAP1.
Structure, 24:2115-2126, 2016

PubMed 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.

PubMed: 27839950
DOI: 10.1016/j.str.2016.10.006

Experimental method

X-RAY DIFFRACTION (2.55 Å)