4JMH

Crystal structure of synthetic protein in complex with double pY peptide

4JMH の概要

• エントリーDOI: 10.2210/pdb4jmh/pdb
• 関連するPDBエントリー: 4JMG
• 分子名称: Clamp Shc1_pY239/240, SHC-transforming protein 1 (3 entities in total)
• 機能のキーワード: synthetic protein, binding to double py containing sequence, de novo protein
• 由来する生物種: synthetic construct; 詳細
• 細胞内の位置: Cytoplasm. Isoform p46Shc: Mitochondrion matrix. Isoform p66Shc: Mitochondrion (By similarity): P29353
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24073.54

構造登録者

Yasui, N.,Smith, L.,Koide, S. (登録日: 2013-03-14, 公開日: 2014-04-23, 最終更新日: 2024-11-20)

主引用文献

Yasui, N.,Findlay, G.M.,Gish, G.D.,Hsiung, M.S.,Huang, J.,Tucholska, M.,Taylor, L.,Smith, L.,Boldridge, W.C.,Koide, A.,Pawson, T.,Koide, S.
Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation.
Mol.Cell, 54:1034-1041, 2014

PubMed Abstract: Cell signaling depends on dynamic protein-protein interaction (PPI) networks, often assembled through modular domains each interacting with multiple peptide motifs. This complexity raises a conceptual challenge, namely to define whether a particular cellular response requires assembly of the complete PPI network of interest or can be driven by a specific interaction. To address this issue, we designed variants of the Grb2 SH2 domain ("pY-clamps") whose specificity is highly biased toward a single phosphotyrosine (pY) motif among many potential pYXNX Grb2-binding sites. Surprisingly, directing Grb2 predominantly to a single pY site of the Ptpn11/Shp2 phosphatase, but not other sites tested, was sufficient for differentiation of the essential primitive endoderm lineage from embryonic stem cells. Our data suggest that discrete connections within complex PPI networks can underpin regulation of particular biological events. We propose that this directed wiring approach will be of general utility in functionally annotating specific PPIs.

PubMed: 24910098
DOI: 10.1016/j.molcel.2014.05.002

実験手法

X-RAY DIFFRACTION (2.408 Å)