Prediction of multidimensional heteronuclear NOESY spectra and NMR structure determination
My research focuses on applying NMR to the structural determination of biomolecules. The double phosyphorylation of Tyr 342 and Tyr 346 in Syk is thought to be involved in the Syk-dependent signaling pathway in B cells. Based on the pull-down experiment, phospholipase C-γ, Vav, Fgr, and Lck proteins have high affinities with the Syk by the interaction of the Src homology 2 domains and doubly phosphorylated-tyrosine peptide motifs (pYpY). The structure of c-terminal SH2 domain of phospholipase C-γ (PLCC-SH2) with pYpY peptide was solved by our former group member. SH2 domains contain a central anti-parallel β sheet flanked by two α helices. The NMR structure of the PLCC-SH2 complex shows a induced-fit conformational change when the SH2 domain binds to pYpY peptide, which does not occur in other known SH2 complexes. I am working on determining the SH2 domain structure of Vav1 proteins which is also expected to bind to the pYpY peptide. We wonder whether they undergo the same conformational changes during the pYpY binding. I am also interested in the structure-based NOESY assignment that has the potential for improving ambiguous and automatic NOESY assignment.