2OZO

Autoinhibited intact human ZAP-70

Summary for 2OZO

• Entry DOI: 10.2210/pdb2ozo/pdb
• Descriptor: Tyrosine-protein kinase ZAP-70, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: inactive zap-70, tandem sh2, autoinhibition, itam, hydrogen bonding network, tcr signaling, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): P43403
• Total number of polymer chains: 1
• Total formula weight: 69879.16

Authors

Deindl, S.,Kadlecek, T.A.,Brdicka, T.,Cao, X.,Weiss, A.,Kuriyan, J. (deposition date: 2007-02-26, release date: 2007-05-22, Last modification date: 2024-02-21)

Primary citation

Deindl, S.,Kadlecek, T.A.,Brdicka, T.,Cao, X.,Weiss, A.,Kuriyan, J.
Structural Basis for the Inhibition of Tyrosine Kinase Activity of ZAP-70.
Cell(Cambridge,Mass.), 129:735-746, 2007

PubMed Abstract: 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.

PubMed: 17512407
DOI: 10.1016/j.cell.2007.03.039

Experimental method

X-RAY DIFFRACTION (2.6 Å)