2MRK

Fyn SH2 domain in complex with the natural inhibitory phosphotyrosine peptide

2MRK の概要

• エントリーDOI: 10.2210/pdb2mrk/pdb
• 関連するPDBエントリー: 2mqi 2mrj
• NMR情報: BMRB: 25082
• 分子名称: Tyrosine-protein kinase Fyn, C-terminal Tyrosine-protein kinase Fyn (2 entities in total)
• 機能のキーワード: phosphorylated peptide, fyn kinase, sh2 domain, src kinase, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P06241 P06241
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12944.54

構造登録者

Huculeci, R.,Buts, L.,Lenaerts, A.J.,van Nuland, N. (登録日: 2014-07-09, 公開日: 2015-07-15, 最終更新日: 2024-11-20)

主引用文献

Huculeci, R.,Cilia, E.,Lyczek, A.,Buts, L.,Houben, K.,Seeliger, M.A.,van Nuland, N.,Lenaerts, T.
Dynamically Coupled Residues within the SH2 Domain of FYN Are Key to Unlocking Its Activity.
Structure, 24:1947-1959, 2016

PubMed Abstract: Src kinase activity is controlled by various mechanisms involving a coordinated movement of kinase and regulatory domains. Notwithstanding the extensive knowledge related to the backbone dynamics, little is known about the more subtle side-chain dynamics within the regulatory domains and their role in the activation process. Here, we show through experimental methyl dynamic results and predicted changes in side-chain conformational couplings that the SH2 structure of Fyn contains a dynamic network capable of propagating binding information. We reveal that binding the phosphorylated tail of Fyn perturbs a residue cluster near the linker connecting the SH2 and SH3 domains of Fyn, which is known to be relevant in the regulation of the activity of Fyn. Biochemical perturbation experiments validate that those residues are essential for inhibition of Fyn, leading to a gain of function upon mutation. These findings reveal how side-chain dynamics may facilitate the allosteric regulation of the different members of the Src kinase family.

PubMed: 27692963
DOI: 10.1016/j.str.2016.08.016

実験手法

SOLUTION NMR