Controlling amyloid growth in multiple dimensions.
The great progress made in defining the structure of protein and peptide amyloid assemblies, particularly the arrangement of peptides in beta-sheets, is counterbalanced by the still poor understanding of the higher organization of beta-sheets within the fibril and overall fibril/fibril associations. The assembly pathway and basis of amyloid toxicity may well depend on these higher-order structural features. For example, significant evidence points to association between sheets as the rate limiting step in fibril assembly, and a critical metal binding site has now been identified that involves residues from different individual sheets. Here we review experiments that are identifying some of the issues associated with sheet-sheet association by investigating simple model peptides derived from the central core of the Abeta peptide implicated in Alzheimer's disease. These peptides transit between fibril/ribbon/nanotube morphologies in response to assembly conditions, laying the foundation for understanding the folding landscape for these higher order assemblies, revealing potential targets for therapeutic intervention, and opening strategies for the design of highly ordered peptide self-assembled microscale morphologies.
Dong
Jijun
J
Center for the Analysis of Supramolecular Self-assemblies, Departments of Chemistry and Biology, Emory University, Atlanta, GA 30322, USA.
Lu
Kun
K
Lakdawala
Ami
A
Mehta
Anil K
AK
Lynn
David G
DG
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D015032:Zinc / Q000378:metabolism
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C407125:amyloid beta-protein (10-35); C417223:amyloid beta-protein (16-22); D015032:Zinc