Title : Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker.

Pub. Date : 2013 Jun

PMID : 23530057






7 Functional Relationships(s)
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1 We previously reported the structure of an autoinhibited ZAP-70 variant in which two regulatory tyrosine residues (315 and 319) in the SH2-kinase linker were replaced by phenylalanine. Tyrosine zeta chain of T cell receptor associated protein kinase 70 Homo sapiens
2 We now present a crystal structure of ZAP-70 in which Tyr 315 and Tyr 319 are not mutated, leading to the recognition of a five-residue sequence register error in the SH2-kinase linker of the original crystallographic model. Tyrosine zeta chain of T cell receptor associated protein kinase 70 Homo sapiens
3 We now present a crystal structure of ZAP-70 in which Tyr 315 and Tyr 319 are not mutated, leading to the recognition of a five-residue sequence register error in the SH2-kinase linker of the original crystallographic model. Tyrosine zeta chain of T cell receptor associated protein kinase 70 Homo sapiens
4 As seen in a recently reported structure of the related tyrosine kinase Syk, Tyr 315 of ZAP-70 is part of a hydrophobic interface between the regulatory apparatus and the kinase domain, and the integrity of this interface would be lost upon engagement of doubly phosphorylated peptides by the SH2 domains. Tyrosine zeta chain of T cell receptor associated protein kinase 70 Homo sapiens
5 Tyr 319 is not necessarily dislodged by SH2 engagement, which activates ZAP-70 only ~5-fold in vitro. Tyrosine zeta chain of T cell receptor associated protein kinase 70 Homo sapiens
6 This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck. Tyrosine zeta chain of T cell receptor associated protein kinase 70 Homo sapiens
7 This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck. Tyrosine zeta chain of T cell receptor associated protein kinase 70 Homo sapiens