2ozo
From Proteopedia
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==Overview== | ==Overview== | ||
| - | ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor | + | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176947 176947]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Cao, X.]] | [[Category: Cao, X.]] | ||
[[Category: Deindl, S.]] | [[Category: Deindl, S.]] | ||
| - | [[Category: Kadlecek, T | + | [[Category: Kadlecek, T A.]] |
[[Category: Kuriyan, J.]] | [[Category: Kuriyan, J.]] | ||
[[Category: Weiss, A.]] | [[Category: Weiss, A.]] | ||
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[[Category: tcr signaling]] | [[Category: tcr signaling]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:16 2008'' |
Revision as of 16:24, 21 February 2008
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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 and 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 Thu Feb 21 18:24:16 2008
