Structural basis of ZAP-70 activation upon phosphorylation of tyrosines 315, 319 and 493

Abstract

ZAP-70 (Zeta-chain-Associated Protein kinase 70) is a key kinase in the regulation of the adaptive immune response. Zap-70 acts by binding its SH2-domains to the T-cell-associated CD3ζ protein, thus transmitting a T-cell activation signal induced by the interaction of Major Histocompatibility Complex with T-cell Receptor. It has been established that for ZAP-70 kinase activation, the phosphorylation of Tyr315, Tyr319, and Tyr493 is required, however the mechanisms are unclear. In the present study, we use the tools of structural modeling to elucidate the ZAP-70 activation mechanisms.