Structural Basis of Signal Transduction
This course is focused on the structure-function relationship of key enzymes and protein assemblies in signal transduction (protein/lipid kinases, phosphatases, ubiquitin ligases, GPCRs and G-proteins, etc.). The main theme of this course is to appreciate how structural/conformational changes lead to critical functional/signaling switches.
There are three learning objectives.
- By the end of the course, students are expected to know the common structural features and signaling/regulatory principles of most important signaling protein families, including kinases, phosphatases, ubiquitin ligases, G-proteins and GPCRs.
- Through structural analysis, students are expected to learn ways to design approaches to specifically manipulate or control these molecular systems.
- Through homework and discussions, students are required to be able to download PBD files, analyze the molecular structure (using program such as Pymol), and obtain desired structure-function relationship information.
In addition to attending all classes, students are required to present one paper and complete one homework. The final grade results from: 40% class participation (attendance and discussion); 30% presentation (graded by students); 30% home work.
|1||Course organization; Introductions to cell signaling and protein structure; Visualization and analysis of protein structures by Pymol.||Classification, structural topology and active sites of protein kinases; Protein kinase inhibitors; inhibitor development; Chemical genetics: an example of using specific kinase inhibitors|
|2||Structural motifs that specifically recognize phosphorylated protein; pY evolution; Protein activity regulation by intra- and intermolecular interactions: Src Structure and regulation of protein phosphatases; Substrate trapping strategy; phosphatase inhibitors (cyclosporine, FK506 and beyond)||Signaling by Small G-proteins, GEF, GAP and down stream effectors|
|3||Protein degradation by the ubiquitin ligase/proteosome system, Cell regulation via large protein assemblies||Structure and signaling of G-protein coupled receptors (GPCR) and homology-based structure modeling|
|4||Second messenger signaling: phosphatidylinositol, cAMP, cGMP and Ca++ Intracellular signaling; Chemical genetics: induced dimerization and controlled protein functions||Student presentation/discussion #1-6|
|5||Student presentation/discussion #7-12||Student presentation/discussion #13-17|