Chemical catalysis by biological amyloids.

ABSTRACT

Toxic aggregation of proteins and peptides into amyloid fibers is the basis of several human diseases. In each disease, a particular peptide noncovalently assembles into long thin structures with an overall cross-ß fold. Amyloids are not only related to disease functional amyloids are found in many biological systems and artificial peptide amyloids are developed into novel nanomaterials. Amyloid fibers can act as template for the generation of more amyloids but are considered nonreactive in chemical catalysis. The perception of amyloids as chemically inert species was recently challenged by in vitro work on three human amyloid systems. With the use of model substrates, amyloid-ß, α-synuclein and glucagon amyloids were found to catalyze biologically relevant chemical reactions. The detected catalytic activity was much less than that of 'real' enzymes, but like that of designed (synthetic) catalytic amyloids. I here describe the current knowledge around this new activity of natural amyloids and the putative connection to metabolic changes in amyloid diseases. These pioneering studies imply that catalytic activity is an unexplored gain-of-function activity of disease amyloids. In fact, all biological amyloids may harbor intrinsic catalytic activity, tuned by each amyloid's particular fold, that await discovery.