Structural Basis of Signal Transduction

Course Number: 
CONJ 524
Course Type: 
Elective
Currently Offered: 
Yes
Credits: 
1.5
Quarter: 
Winter
Weeks: 
6-10
Meeting Time: 
T Th 1:00-2:30
Location: 
UW
Instructor (MCB Faculty): 
Xu, Wenqing
Class Size: 
20
Course Description: 

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.

Learning Objectives: 

There are three learning objectives. 

  1. 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.   
  2. Through structural analysis, students are expected to learn ways to design approaches to specifically manipulate or control these molecular systems.  
  3. 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. 
Prerequisites: 
Undergraduate biochemistry and basic cell biology.
Course requirements, examinations and grading: 

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.

Sample Schedule:
Week Tues Thurs
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
Areas of Interest: 
Molecular Structure & Computational Biology
Elective Area: 
Cancer Biology
Cell Signaling & Cell/Environment Interactions
Molecular Structure & Computational Biology