5MK2

Crystal structure of the His Domain Protein Tyrosine Phosphatase (HD-PTP/PTPN23) Bro1 domain (CHMP4B peptide complex structure)

5MK2 の概要

• エントリーDOI: 10.2210/pdb5mk2/pdb
• 分子名称: Tyrosine-protein phosphatase non-receptor type 23, Charged multivesicular body protein 4b (3 entities in total)
• 機能のキーワード: escrt-iii chmp4b, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 83856.52

構造登録者

Levy, C.,Gahloth, D. (登録日: 2016-12-02, 公開日: 2017-08-16, 最終更新日: 2024-01-17)

主引用文献

Gahloth, D.,Levy, C.,Walker, L.,Wunderley, L.,Mould, A.P.,Taylor, S.,Woodman, P.,Tabernero, L.
Structural Basis for Specific Interaction of TGF beta Signaling Regulators SARA/Endofin with HD-PTP.
Structure, 25:1011-1024.e4, 2017

PubMed Abstract: SARA and endofin are endosomal adaptor proteins that drive Smad phosphorylation by ligand-activated transforming growth factor β/bone morphogenetic protein (TGFβ/BMP) receptors. We show in this study that SARA and endofin also recruit the tumor supressor HD-PTP, a master regulator of endosomal sorting and ESCRT-dependent receptor downregulation. High-affinity interactions occur between the SARA/endofin N termini, and the conserved hydrophobic region in the HD-PTP Bro1 domain that binds CHMP4/ESCRT-III. CHMP4 engagement is a universal feature of Bro1 proteins, but SARA/endofin binding is specific to HD-PTP. Crystallographic structures of HD-PTP in complex with SARA, endofin, and three CHMP4 isoforms revealed that all ligands bind similarly to the conserved site but, critically, only SARA/endofin interact at a neighboring pocket unique to HD-PTP. The structures, together with mutagenesis and binding analysis, explain the high affinity and specific binding of SARA/endofin, and why they compete so effectively with CHMP4. Our data invoke models for how endocytic regulation of TGFβ/BMP signaling is controlled.

PubMed: 28602823
DOI: 10.1016/j.str.2017.05.005

実験手法

X-RAY DIFFRACTION (1.7 Å)