As one of the most abundant protein-protein interaction module in the eukaryotic genomes, PDZ domain participates in a variety of cellular activities including neuronal signal transduction, protein trafficking, epithelial cell-cell adhesion. And also, PDZ-containing proteins play critical role in the control of macromolecular complex assembly and targeting within cells for different cellular events. To better understand domains function, in the first part, I use NMR spectroscopy to determine the atomic three-dimensional structures of MAGI-3 PDZ4, which revealed to be a canonical PDZ domain and can bind to the type-I binding motif. Further characterization showed that MAGI-3 PDZ4 can interact with the COOH termini tail of Cadherin23. The study of MAGI-3 PDZ4 and Cadherin23 COOH termini t...[ Read more ]

As one of the most abundant protein-protein interaction module in the eukaryotic genomes, PDZ domain participates in a variety of cellular activities including neuronal signal transduction, protein trafficking, epithelial cell-cell adhesion. And also, PDZ-containing proteins play critical role in the control of macromolecular complex assembly and targeting within cells for different cellular events. To better understand domains function, in the first part, I use NMR spectroscopy to determine the atomic three-dimensional structures of MAGI-3 PDZ4, which revealed to be a canonical PDZ domain and can bind to the type-I binding motif. Further characterization showed that MAGI-3 PDZ4 can interact with the COOH termini tail of Cadherin23. The study of MAGI-3 PDZ4 and Cadherin23 COOH termini tail indicates that MAGI-3 may present as a component of tip link and regulate the function of Cadherin23.

The second part of this dissertation describes the biochemical and structural study of BDNF prodomain with its implication in regulation the function of mature BDNF since the mature BDNF and proBDNF play the distinct function in different neuronal process. NMR spectroscopy was used again to calculate the 3D atomic structure of BDNF prodomain. The structure showed that BDNF prodomain exists in a very flexible and dynamic state in solution and the prodomain has quite weak interaction with the mature BDNF.