6ZEH

Structure of PP1-spectrin alpha II chimera [PP1(7-304) + linker (G/S)x9 + spectrin alpha II (1025-1039)] bound to Phactr1 (516-580)

6ZEH の概要

• エントリーDOI: 10.2210/pdb6zeh/pdb
• 分子名称: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit,Spectrin alpha chain, non-erythrocytic 1, Phosphatase and actin regulator, MANGANESE (II) ION, ... (6 entities in total)
• 機能のキーワード: pp1, phosphatase, phactr, rpel, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 92137.56

構造登録者

Mouilleron, S.,Treisman, R.,Fedoryshchak, R.,Lee, R.,Butler, A.M.,Prechova, M. (登録日: 2020-06-16, 公開日: 2020-09-30, 最終更新日: 2024-01-24)

主引用文献

Fedoryshchak, R.O.,Prechova, M.,Butler, A.,Lee, R.,O'Reilly, N.,Flynn, H.R.,Snijders, A.P.,Eder, N.,Ultanir, S.,Mouilleron, S.,Treisman, R.
Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme.
Elife, 9:-, 2020

PubMed Abstract: PPP-family phosphatases such as PP1 have little intrinsic specificity. Cofactors can target PP1 to substrates or subcellular locations, but it remains unclear how they might confer sequence-specificity on PP1. The cytoskeletal regulator Phactr1 is a neuronally enriched PP1 cofactor that is controlled by G-actin. Structural analysis showed that Phactr1 binding remodels PP1's hydrophobic groove, creating a new composite surface adjacent to the catalytic site. Using phosphoproteomics, we identified mouse fibroblast and neuronal Phactr1/PP1 substrates, which include cytoskeletal components and regulators. We determined high-resolution structures of Phactr1/PP1 bound to the dephosphorylated forms of its substrates IRSp53 and spectrin αII. Inversion of the phosphate in these holoenzyme-product complexes supports the proposed PPP-family catalytic mechanism. Substrate sequences C-terminal to the dephosphorylation site make intimate contacts with the composite Phactr1/PP1 surface, which are required for efficient dephosphorylation. Sequence specificity explains why Phactr1/PP1 exhibits orders-of-magnitude enhanced reactivity towards its substrates, compared to apo-PP1 or other PP1 holoenzymes.

PubMed: 32975518
DOI: 10.7554/eLife.61509

実験手法

X-RAY DIFFRACTION (1.3 Å)