2020-2021 Faculty Research Grants
Peter Lyons (Biology)
Structure and Function of Carboxypeptidase O: A Unique Metalloprotease
The structure and function of a protein is determined by its sequence of amino acids. This sequence can be changed through a variety of modifications including proteolysis, the cutting of the amino acid chain by a protease to create a shorter chain, which commonly leads to large changes in protein function. We aim to investigate the function of one such protease, carboxypeptidase O, through experiments looking at its protein structure, its gene structure, and its cellular function. This three-part approach will allow the continued involvement of a number of students in projects leading to publication. In the first part, the unique structure of CPO will be examined, lacking a prodomain necessary for other related proteins to fold properly. We have previously identified amino acids unique to CPO that appear important for folding. We will swap these amino acids into the related CPA1, and examine the subsequent stability of this protein with and without its prodomain. Secondly, the increased level of gene duplication observed for the CPO gene (4 times greater than other related genes) will be examined. In addition to bioinformatics analysis, we will investigate the functionality of these CPO copies as found in the model organism, Xenopus tropicalis. Finally, a potential role for CPO in regulating immune cell growth through control of folate absorption will be investigated, through in vitro binding assays as well as the examination of CPO expression in a cultured immune cell line.