7SA7

Crystal structure of the apo SH2 domains of Syk

7SA7 の概要

• エントリーDOI: 10.2210/pdb7sa7/pdb
• 分子名称: Tyrosine-protein kinase SYK (2 entities in total)
• 機能のキーワード: kinase, sh2 domain, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 180673.27

構造登録者

Hobbs, H.T.,Badroos, J.,Gee, C.L.,Kuriyan, J. (登録日: 2021-09-22, 公開日: 2021-10-13, 最終更新日: 2023-10-18)

主引用文献

Hobbs, H.T.,Shah, N.H.,Badroos, J.M.,Gee, C.L.,Marqusee, S.,Kuriyan, J.
Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases.
Protein Sci., 30:2373-2384, 2021

PubMed Abstract: The catalytic activity of Syk-family tyrosine kinases is regulated by a tandem Src homology 2 module (tSH2 module). In the autoinhibited state, this module adopts a conformation that stabilizes an inactive conformation of the kinase domain. The binding of the tSH2 module to phosphorylated immunoreceptor tyrosine-based activation motifs necessitates a conformational change, thereby relieving kinase inhibition and promoting activation. We determined the crystal structure of the isolated tSH2 module of Syk and find, in contrast to ZAP-70, that its conformation more closely resembles that of the peptide-bound state, rather than the autoinhibited state. Hydrogen-deuterium exchange by mass spectrometry, as well as molecular dynamics simulations, reveal that the dynamics of the tSH2 modules of Syk and ZAP-70 differ, with most of these differences occurring in the C-terminal SH2 domain. Our data suggest that the conformational landscapes of the tSH2 modules in Syk and ZAP-70 have been tuned differently, such that the autoinhibited conformation of the Syk tSH2 module is less stable. This feature of Syk likely contributes to its ability to more readily escape autoinhibition when compared to ZAP-70, consistent with tighter control of downstream signaling pathways in T cells.

PubMed: 34601763
DOI: 10.1002/pro.4199

実験手法

X-RAY DIFFRACTION (3.2 Å)