Self assembly of short aromatic peptides into amyloid fibrils and related nanostructures.
The formation of amyloid fibrils is the hallmark of more than twenty human disorders of unrelated etiology. In all these cases, ordered fibrillar protein assemblies with a diameter of 7-10 nm are being observed. In spite of the great clinical important of amyloid-associated diseases, the molecular recognition and self-assembly processes that lead to the formation of the fibrils are not fully understood. One direction to decipher the mechanism of amyloid formation is the use of short peptides fragments as model systems. Short peptide fragments, as short as pentapeptides, were shown to form typical amyloid assemblies in vitro that have ultrastructural, biophysical, and cytotoxic properties, as those of assemblies that are being formed by full length polypeptides. When we analyzed such short fragments, we identified the central role of aromatic moieties in the ability to aggregate into ordered nano-fibrillar structures. This notion allowed us to discover additional very short amyloidogenic peptides as well as other aromatic peptide motifs, which can form various assemblies at the nano-scale (including nanotubes, nanospheres, and macroscopic hydrogels with nano-scale order). Other practical utilization of this concept, together with novel beta breakage methods, is their use for the development of novel classes of amyloid formation inhibitors.
Gazit
Ehud
E
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. ehudg@post.tau.ac.il
D020816:Amino Acid Motifs; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D006801:Humans; D008954:Models, Biological; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary
D000682:Amyloid; D010455:Peptides