University of Connecticut |
Polymer Program SeminarThe Organization and Assembly of a Prion Peptide Aggregate as Probed by Isotope-edited Infrared Spectroscopy Friday, March 19, 2004 11:00 am , IMS Room 20 Insight into the details of protein misfolding diseases requires a detailed understanding of the conformation and dynamics of multi-strand $B&B(B-sheet aggregates. This seminar will describe an isotope-edited FTIR study of a model peptide directed at the elucidation of residue-level details of the structure and assembly mechanism of a $B&B(B-sheet aggregate. A series of specifically isotope-labeled derivatives of short peptides derived from the Syrian hamster prion protein (PrP) have been synthesized and characterized by FTIR. Based on analysis of variable temperature FTIR spectra of these peptides in solution, the organization of strands within the $B&B(B-sheets has been determined. Moreover, we have observed that the peptides initially form a kinetically-trapped intermediate $B&B(B-sheet with a distribution of strand alignments, which can be rearranged into the stable equilibrium conformation by an annealing cycle. In an effort to completely characterize the mechanism of $B&B(B-sheet formation, we have measured the kinetics of these processes as a function of peptide concentration, temperature, and amino acid sequence. Taken as a whole, these studies not only expand our picture of prion peptide aggregation, but also lend insight into more fundamental questions on the mechanism of $B&B(B-sheet formation.
This seminar series is sponsored by generous grants from U.S. Surgical Corporation and Rogers Corporation. |