We have made major findings on the physical properties of this notoriously difficult-to-work-with peptide. Perhaps the most important and surprising result is the discovery in collaboration with Rodolfo Ghirlando using sedimentation equilibrium and velocity that amylin remains monomeric prior and during the formation of amyloid fibers, This is in contrast to the prevailing view in other amyloid-associated diseases that oligomeric species, and not the mature fibrils, are the toxic species. The second is the discovery form end-to-end contact measurements using a triplet quenching technique that non-amyloid forming rat amylin is a much stiffer peptide than human amylin, and may account for the differences in aggregation propensity. Finally, in collaboration with Alex Grishaev,the radius of gyration of amylin, the most fundamental physical property of a disordered peptide, has been determined from small angle X-ray scattering measurements. See annual report by James Hofrichter for additional details.
| Vaiana, Sara M; Ghirlando, Rodolfo; Yau, Wai-Ming et al. (2008) Sedimentation studies on human amylin fail to detect low-molecular-weight oligomers. Biophys J 94:L45-7 |
