2ozo
From Proteopedia
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Autoinhibited intact human ZAP-70
Contents |
Overview
ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor, signaling, is controlled by a regulatory segment that includes a tandem, SH2 unit responsible for binding to immunoreceptor tyrosine-based, activation motifs (ITAMs). The crystal structure of autoinhibited ZAP-70, reveals that the inactive kinase domain adopts a conformation similar to, that of cyclin-dependent kinases and Src kinases. The autoinhibitory, mechanism of ZAP-70 is, however, distinct and involves interactions, between the regulatory segment and the hinge region of the kinase domain, that reduce its flexibility. Two tyrosine residues in the SH2-kinase, linker that activate ZAP-70 when phosphorylated are involved in, aromatic-aromatic interactions that connect the linker to the kinase, domain. These interactions are inconsistent with ITAM binding, suggesting, that destabilization of this autoinhibited ZAP-70 conformation is the, first step in kinase activation.
Disease
Known diseases associated with this structure: Selective T-cell defect OMIM:[176947]
About this Structure
2OZO is a Single protein structure of sequence from Homo sapiens with MG and ANP as ligands. Active as Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Structural basis for the inhibition of tyrosine kinase activity of ZAP-70., Deindl S, Kadlecek TA, Brdicka T, Cao X, Weiss A, Kuriyan J, Cell. 2007 May 18;129(4):735-46. PMID:17512407
Page seeded by OCA on Mon Nov 12 23:18:39 2007
