CAA: Spectroscopic Analysis of the Tryptophan Residues of the BTK-SH3 Domain

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The SH3 domain is a conserved sequence ~70 amino acids involved in signaling pathways through interactions with proline-rich peptides. The goal of this Career Advancement Award (CAA) research project is to investigate the specific roles of two conserved tryptophan residues of the Bruton's tyrosine kinase SH3 domain (BTK-SH3) in the interaction with proline rich peptides. To achieve this goal, BTK-SH3 domain wild type and single amino acid mutants will be characterized using circular dichroism (CD), fluorescence and Raman spectroscopies, which will elucidate protein structural changes upon complex formation between the SH3 domain and the proline-rich peptides. Raman spectroscopy will determine microenvironmental changes in the tryptophan vicinity due to the interaction between BTK-SH3 and the proline-rich peptides. The proposed studies will delineate the role of the conserved tryptophan residues of the BTK-SH3 domain at the molecular level and their significance in the interaction of the BTK-SH3 domain with regulating proline-rich peptides. The results from these studies will be critical in building a broad and long-term research project in analysis of SH3 domains using biophysical techniques.Broader impacts: This project will open the doors of laboratory research to underrepresented students and aid in increasing the retention of such students at the undergraduate level. To accomplish this task, two activities will be undertaken: a summer experience in science for college minority students and a weeklong science experience for 4th-6th and 7th-9th graders. The experience for the college students will allow them to participate in this project during the summer and academic year. Students will participate in research, seminars, workshops on communication and visits to other research facilities within Virginia. Students will present their research results in local, regional and national scientific meetings. The participants of the weeklong summer science experience will enjoy classroom and laboratory activities appropriate for their age. Students will enhance their mathematical and science knowledge and skills. Through these activities the students will know first hand what it is to work in a laboratory and will be exposed to different aspects of science. The end goal of these activities is to attract students from underrepresented backgrounds to obtain undergraduate degrees in biological and chemical sciences.