On Going Research

The cytoplasmic tyrosine kinase (Bruton's tyrosine kinase, BTK) was found to play a central role for B cell development. Mutations or deletions within this protein are responsible for X-linked agammagobulinemia (XLA), an inherited immunodeficiency decease. BTK contains an apparent pleckstrin homology (PH) domain, a Src homology 2 (SH2) domain, a SH3 domain and a catalytic tyrosine kinase domain. SH2 and SH3 domains are small protein modules that mediate protein-protein interactoins and are found in many proteins involved in intracellular signal transduction. In order to investigate the role of BTK in B cell development and activation, we are applying multi-dimensional NMR techniques to study structures of the SH2 and SH3 domains of BTK. Peptide libraries will be collected to reveal novel binding ligands for the SH2 and SH3 domains of BTK. Structural studies of the ligand/SH2 and ligand/SH3 complexes will be carried out and new ligands can be designed through a rational approach.

Integration of human immunodeficiency virus (HIV) DNA into the host genome is an essential step for the virus. There is only a single protein, the HIV integrase (IN), required to cleave two nucleotides from both 3' viral DNA ends and integrate the recessed viral DNA to the host genome. IN has a molecular weight of 35 KD and contains at least four functional domains, an N-terminal zinc finger domain, a central catalytic domain, a predicted leucine zipper domain, and a non-specific DNA binding domain. In order to understand the mechanism of integration and the role of these functional domains, the structure of the leucine zipper domain and non-specific DNA binding domain will be studied first. Structure of the DNA binding domain and its complex with viral DNA will also be studied using isotope-editing techniques.