{"entity": "publication", "iuid": "d2bf357928a048d687cc6a87e19ef31c", "timestamp": "2026-05-09T17:35:27.285Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d2bf357928a048d687cc6a87e19ef31c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d2bf357928a048d687cc6a87e19ef31c"}}, "title": "Structural basis for the inhibition of tyrosine kinase activity of ZAP-70.", "authors": [{"family": "Deindl", "given": "Sebastian", "initials": "S"}, {"family": "Kadlecek", "given": "Theresa A", "initials": "TA"}, {"family": "Brdicka", "given": "Tomas", "initials": "T"}, {"family": "Cao", "given": "Xiaoxian", "initials": "X"}, {"family": "Weiss", "given": "Arthur", "initials": "A"}, {"family": "Kuriyan", "given": "John", "initials": "J"}], "type": "journal article", "published": "2007-05-18", "journal": {"title": "Cell", "issn": "0092-8674", "volume": "129", "issue": "4", "pages": "735-746", "issn-l": null}, "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.", "doi": "10.1016/j.cell.2007.03.039", "pmid": "17512407", "labels": {"Sebastian Deindl": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "S0092-8674(07)00455-2"}], "notes": [], "created": "2020-10-09T09:53:54.796Z", "modified": "2022-11-07T11:37:50.965Z"}