2ozo: Difference between revisions

Line 4:

==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.

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==

Line 17:

Line 20:

[[Category: Cao, X.]]

[[Category: Deindl, S.]]

[[Category: Kadlecek, T.A.]]

[[Category: Kadlecek, T A.]]

[[Category: Kuriyan, J.]]

[[Category: Weiss, A.]]

Line 29:

Line 32:

[[Category: tcr signaling]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 23 14~~:59:18 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:16 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 17: / Line 20: @@
 [[Category: Cao, X.]]
 [[Category: Deindl, S.]]
-[[Category: Kadlecek, T.A.]]
+[[Category: Kadlecek, T A.]]
 [[Category: Kuriyan, J.]]
 [[Category: Weiss, A.]]
@@ Line 29: / Line 32: @@
 [[Category: tcr signaling]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:59:18 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:16 2008''