丁香园AV

Synopsis

Proteins can fold, unfold, misfold and aggregate into various forms, including well-organized amyloid fibrils. Certain amyloids are associated with disease (e.g. prions, Alzheimer鈥檚 and Parkinson鈥檚), while others serve a natural, functional role. Thirdly, engineered amyloid fibrils, or nanofibrils, have potential applications ranging from nanowires and cell scaffolding to food ingredients. We鈥檝e examined nanofibrils derived from legume seed storage proteins as potential sustainable materials for food and materials applications. We discovered that legume proteins are abundant in amyloid regions, using LC-MS/MS and bioinformatics to characterize the fibril-core peptides from various legumes, and characterized their structure-function relationships. Another major focus is functional amyloid, CsgA, that forms a critical part of bacterial biofilm and thus is a novel antimicrobial target. Monomeric CsgA is intrinsically disordered and highly aggregation prone, confounding high-resolution studies of its structure and amyloid formation mechanism. We are using a combination of single-molecule force spectroscopy (with optical tweezers) and cryoEM to define the assembly mechanism from single protein molecules to mature fibres. So far, we have studied single molecules of monomeric and dimeric CsgA, revealing novel dynamic behaviour, and solved the 3.6 脜 structure of CsgA fibrils. Hopefully these studies will help us better understand amyloid formation in order to prevent disease-associated amyloid and to improve engineered amyloid.