Crystallization of Analog-sensitive ZAP-70 with a Genetically Modified Inhibitor
My research is focused on a protein tyrosine kinase called Zeta-associated protein of 70kDa (ZAP-70), which plays a crucial role in initiating T-cell signaling. An inhibitor specific for ZAP-70 would be clinically significant in treating autoimmune diseases via downregulation of signaling in T-cells that attack the bodys own cells. Our collaborator at UCSF, Arthur Weiss, is using chemical genetics to study ZAP-70s role in T-cell signaling and development. The Weiss lab has developed a mutant version of ZAP-70 that can be selectively inhibited by a derivatized kinase inhibitor. My goal is to crystallize the analog sensitive ZAP-70 with the specific inhibitor bound to it. A structure of this would reveal in molecular detail how the inhibitor binds. This would allow the design of more potent inhibitors, which are necessary for use in the animal studies that the Weiss lab would like to pursue.
Message to Sponsor
- Major: Bioengineering
- Sponsor: Rose Hills Foundation
- Mentor: John Kuriyan, Molecular and Cell Biology and Chemistry