Class of 2007
daotp@jhu.edu | B.A. Biophysics & Molecular Biology, Whitman College
Research
Repeats proteins, comprised of a simple array of like structures and lacking interactions between distant residues as seen with globular proteins, are ideal candidates for folding studies in terms of distribution of local stability, molecular origins of cooperativity and the effects of cooperativity on folding kinetics. The Barrick lab has taken it one step further with consensus ankyrin repeat proteins, with repeats having not only similar secondary and tertiary structures but also nearly identical primary sequences. By fitting a nearest-neighbor (Isling) statistical thermodynamic model to the data, we can significantly learn about intrinsic and interfacial interactions. My project, in collaboration with Tural Askel, another member of the lab, involves applying the same principles to consensus Leucine-rich repeat (LRR) proteins.
Many LRR proteins also have N- and C-terminal capping motifs, which differ in sequences and structures from the repeats. We aim to understand the roles of these motifs in folding of LRR proteins by looking at the effects of various perturbations to the system both thermodynamically and kinetically. For this, we use the naturally occurring LRR domain of tumor suppressor protein PP32.
Publications
Burgess, N.K., T.P. Dao, A.M. Stanley, and K.G. Fleming. (2008) Beta-barrel proteins that reside in the E. coli outer membrane in vivo demonstrate varied folding behavior in vitro. J. Biol. Chem. 283:26748-26758. |
