4XI2

Crystal Structure of an auto-inhibited form of Bruton's Tryrosine Kinase

4XI2 の概要

• エントリーDOI: 10.2210/pdb4xi2/pdb
• 分子名称: Tyrosine-protein kinase BTK, GOLD ION (2 entities in total)
• 機能のキーワード: kinase, phosphorylation, auto-inhibited, b-cell development, x-linked agammaglobulinemia, transferase
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Cytoplasm : P35991
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52192.75

構造登録者

Vogan, E.M.,Harrison, S.C. (登録日: 2015-01-06, 公開日: 2015-02-25, 最終更新日: 2024-02-28)

主引用文献

Wang, Q.,Vogan, E.M.,Nocka, L.M.,Rosen, C.E.,Zorn, J.A.,Harrison, S.C.,Kuriyan, J.
Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate.
Elife, 4:-, 2015

PubMed Abstract: Bruton's tyrosine kinase (Btk), a Tec-family tyrosine kinase, is essential for B-cell function. We present crystallographic and biochemical analyses of Btk, which together reveal molecular details of its autoinhibition and activation. Autoinhibited Btk adopts a compact conformation like that of inactive c-Src and c-Abl. A lipid-binding PH-TH module, unique to Tec kinases, acts in conjunction with the SH2 and SH3 domains to stabilize the inactive conformation. In addition to the expected activation of Btk by membranes containing phosphatidylinositol triphosphate (PIP3), we found that inositol hexakisphosphate (IP6), a soluble signaling molecule found in both animal and plant cells, also activates Btk. This activation is a consequence of a transient PH-TH dimerization induced by IP6, which promotes transphosphorylation of the kinase domains. Sequence comparisons with other Tec-family kinases suggest that activation by IP6 is unique to Btk.

PubMed: 25699547
DOI: 10.7554/eLife.06074

実験手法

X-RAY DIFFRACTION (2.6 Å)