6F3F

Autoinhibited Src kinase bound to ADP

6F3F の概要

• エントリーDOI: 10.2210/pdb6f3f/pdb
• 分子名称: Tyrosine-protein kinase, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: kinase, adp, autoinhibited, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52489.42

構造登録者

von Raussendorf, F.,Leonard, T.A. (登録日: 2017-11-28, 公開日: 2017-12-27, 最終更新日: 2024-10-23)

主引用文献

von Raussendorf, F.,de Ruiter, A.,Leonard, T.A.
A switch in nucleotide affinity governs activation of the Src and Tec family kinases.
Sci Rep, 7:17405-17405, 2017

PubMed Abstract: The Tec kinases, closely related to Src family kinases, are essential for lymphocyte function in the adaptive immune system. Whilst the Src and Abl kinases are regulated by tail phosphorylation and N-terminal myristoylation respectively, the Tec kinases are notable for the absence of either regulatory element. We have found that the inactive conformations of the Tec kinase Itk and Src preferentially bind ADP over ATP, stabilising both proteins. We demonstrate that Itk adopts the same conformation as Src and that the autoinhibited conformation of Src is independent of its C-terminal tail. Allosteric activation of both Itk and Src depends critically on the disruption of a conserved hydrophobic stack that accompanies regulatory domain displacement. We show that a conformational switch permits the exchange of ADP for ATP, leading to efficient autophosphorylation and full activation. In summary, we propose a universal mechanism for the activation and autoinhibition of the Src and Tec kinases.

PubMed: 29234112
DOI: 10.1038/s41598-017-17703-5

実験手法

X-RAY DIFFRACTION (2.41795770496 Å)