5LM2

Crystal Structure of HD-PTP phosphatase

5LM2 の概要

• エントリーDOI: 10.2210/pdb5lm2/pdb
• 分子名称: Tyrosine-protein phosphatase non-receptor type 23 (2 entities in total)
• 機能のキーワード: coiled coil, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: Q9H3S7
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81450.62

構造登録者

Levy, C. (登録日: 2016-07-28, 公開日: 2016-11-30, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.54 Å)