Synaptic Signal Transduction Organization by PDZ-domain Containing Proteins

 

Mingjie Zhang

 

Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong

 

PDZ (postsynaptic density-95, disc-large, and zonulin-1) domain is one of the most abundant protein interaction modules in eukaryotic genomes. PDZ domain-containing proteins play central roles in organizing signal transduction complexes, clustering membrane receptors, and maintaining cell polarities. A typical PDZ domain contains ~90 amino acid residues, and binds specifically to a short peptide at the extreme carboxyl-end of target proteins. In addition, PDZ domains can also bind to internal sequences that fold in a b-hairpin structure, thereby forming PDZ/PDZ heterodimers. In this talk, I will present structural basis of several PDZ domain-mediated protein-protein interactions found in neuronal synapses. The structure and function relationship of these PDZ proteins was further investigated using a combination of  biochemical and cell biology approaches.