The tyrosine kinase ZAP-70 is a critical part of the pathway to initiate T-cell response. Regulation of ZAP-70 by post-translational modifications is important for normal T-cell response and could be a target of diseases that affect the T-cell such as HIV. Many of the known ZAP-70 modifications occur at sites far from the active site, and their relationship to ZAP-70 function is not well understood. In particular, ZAP-70 appears to be ubiquitinated at several sites, but this ubiquitination does not lead to protein degradation. We use molecular dynamics simulations to explore the mechanism by which different ZAP-70 post-translational modifications can allosterically propagate through the protein and affect activity. Methods from information theory help us to identify conformational coupling between non-adjactent sites on a protein. This may allow us to predict the effect of known ZAP-70 post-translational modifications and identify sites that may have an allosteric effect when modified or mutated.

Mechanisms of ZAP-70 kinase regulation by post-translational modifications

248th National Meeting (2014)

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