1CV9

NMR STUDY OF ITAM PEPTIDE SUBSTRATE

1CV9 の概要

• エントリーDOI: 10.2210/pdb1cv9/pdb
• 分子名称: IG-ALPHA ITAM PEPTIDE (1 entity in total)
• 機能のキーワード: lyn tyrosine kinase, itam, immunoreceptor tyrosine activation motif, peptide substate, immune system
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1433.46

構造登録者

Gaul, B.S.,Harrison, M.L.,Geahlen, R.L.,Post, C.B. (登録日: 1999-08-23, 公開日: 1999-08-31, 最終更新日: 2024-10-16)

主引用文献

Gaul, B.S.,Harrison, M.L.,Geahlen, R.L.,Burton, R.A.,Post, C.B.
Substrate recognition by the Lyn protein-tyrosine kinase. NMR structure of the immunoreceptor tyrosine-based activation motif signaling region of the B cell antigen receptor.
J.Biol.Chem., 275:16174-16182, 2000

PubMed Abstract: The immunoreceptor tyrosine-based activation motif (ITAM) plays a central role in transmembrane signal transduction in hematopoietic cells by mediating responses leading to proliferation and differentiation. An initial signaling event following activation of the B cell antigen receptor is phosphorylation of the CD79a (Ig-alpha) ITAM by Lyn, a Src family protein-tyrosine kinase. To elucidate the structural basis for recognition between the ITAM substrate and activated Lyn kinase, the structure of an ITAM-derived peptide bound to Lyn was determined using exchange-transferred nuclear Overhauser NMR spectroscopy. The bound substrate structure has an irregular helix-like character. Docking based on the NMR data into the active site of the closely related Lck kinase strongly favors ITAM binding in an orientation similar to binding of cyclic AMP-dependent protein kinase rather than that of insulin receptor tyrosine kinase. The model of the complex provides a rationale for conserved ITAM residues, substrate specificity, and suggests that substrate binds only the active conformation of the Src family tyrosine kinase, unlike the ATP cofactor, which can bind the inactive form.

PubMed: 10748115
DOI: 10.1074/jbc.M909044199

実験手法

SOLUTION NMR