2RSY

Solution structure of the SH2 domain of Csk in complex with a phosphopeptide from Cbp

2RSY の概要

• エントリーDOI: 10.2210/pdb2rsy/pdb
• NMR情報: BMRB: 11508
• 分子名称: Tyrosine-protein kinase CSK, Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (2 entities in total)
• 機能のキーワード: sh2 domain, csk, cbp, solution structure, transferase-signaling protein complex, transferase/signaling protein
• 由来する生物種: Rattus norvegicus (rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15736.70

構造登録者

Tanaka, H.,Akagi, K.,Oneyama, C.,Tanaka, M.,Sasaki, Y.,Kanou, T.,Lee, Y.,Yokogawa, D.,Debenecker, M.,Nakagawa, A.,Okada, M.,Ikegami, T. (登録日: 2012-09-10, 公開日: 2013-04-10, 最終更新日: 2024-10-16)

主引用文献

Tanaka, H.,Akagi, K.,Oneyama, C.,Tanaka, M.,Sasaki, Y.,Kanou, T.,Lee, Y.H.,Yokogawa, D.,Dobenecker, M.W.,Nakagawa, A.,Okada, M.,Ikegami, T.
Identification of a new interaction mode between the Src homology 2 domain of C-terminal Src kinase (Csk) and Csk-binding protein/phosphoprotein associated with glycosphingolipid microdomains.
J.Biol.Chem., 288:15240-15254, 2013

PubMed Abstract: Proteins with Src homology 2 (SH2) domains play major roles in tyrosine kinase signaling. Structures of many SH2 domains have been studied, and the regions involved in their interactions with ligands have been elucidated. However, these analyses have been performed using short peptides consisting of phosphotyrosine followed by a few amino acids, which are described as the canonical recognition sites. Here, we report the solution structure of the SH2 domain of C-terminal Src kinase (Csk) in complex with a longer phosphopeptide from the Csk-binding protein (Cbp). This structure, together with biochemical experiments, revealed the existence of a novel binding region in addition to the canonical phosphotyrosine 314-binding site of Cbp. Mutational analysis of this second region in cells showed that both canonical and novel binding sites are required for tumor suppression through the Cbp-Csk interaction. Furthermore, the data indicate an allosteric connection between Cbp binding and Csk activation that arises from residues in the βB/βC loop of the SH2 domain.

PubMed: 23548896
DOI: 10.1074/jbc.M112.439075

実験手法

SOLUTION NMR