蛋白質功能實驗室 Laboratory of Protein Function and Structure
研究領域 Research Interests
Protein structure and function, Enzymology.
My research is concerned with the study of proteins, especially those involved in neuronal functions. The research involved isolation of proteins, determination of their structures and properties, cloning, and expression. The research is basic in nature, but significant relationships between this research and human disease. The research projects include two parts. First is focused on the interactions between the protein phosphatase-1 (PP1) and its regulatory proteins, which play a key role in dopaminergic signal transduction of the brain. My laboratory has identified the mechanism of PP1 regulated by one of its inhibitors, inhibitor-2. Recent studies have led to the elucidation of the first secondary structure of inhibitor-2 by NMR. Our final goals are to better understand the molecular mechanism in regulation of PP1, which may result in the design of drugs capable of mimicking or antagonizing the action of PP1, and the role of PP1 in regulation of neuronal functions. Purification and characterization of the novel PP1-binding proteins will be also included. A second area of research created recently concerns the mechanism in prevention of Ab polymerization and the structural differences of apoE isoforms, both of which are highly associated with the pathogenesis of the Alzheimer's disease (AD). Recently, we have planed to design the photo-sensitive peptides that can block the Ab polymerization. Our aim is to use NMR to elucidate 3-dimensional structure of Ab:peptide complex, providing the targets for design of therapeutic drugs in preventing the development of AD. Three common alleles of human apoE, e2, e3 and e4, are found, differing by a single amino acid substitution in residue-112 and –158 and showing the remarkable differences in their biochemistry, and cellular metabolism and biological functions. In this project, we focus on the structural studies of apoE isoforms by using NMR (collaborated with Dr. Ta-Hsien Lin, at VGH, Taipei). Our goals are to understand the relationship between protein structure and function.