Designed peptides that assemble into cross-α amyloid-like structures.

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TitleDesigned peptides that assemble into cross-α amyloid-like structures.
Publication TypeJournal Article
Year of Publication2018
AuthorsZhang, S-Q, Huang, H, Yang, J, Kratochvil, HT, Lolicato, M, Liu, Y, Shu, X, Liu, L, DeGrado, WF
JournalNat Chem Biol
Date Published2018 09
KeywordsAmyloid, Crystallography, X-Ray, Humans, Kinetics, Models, Molecular, Peptides, Protein Conformation

Amyloids adopt 'cross-β' structures composed of long, twisted fibrils with β-strands running perpendicular to the fibril axis. Recently, a toxic peptide was proposed to form amyloid-like cross-α structures in solution, with a planar bilayer-like assembly observed in the crystal structure. Here we crystallographically characterize designed peptides that assemble into spiraling cross-α amyloid-like structures, which resemble twisted β-amyloid fibrils. The peptides form helical dimers, stabilized by packing of small and apolar residues, and the dimers further assemble into cross-α amyloid-like fibrils with superhelical pitches ranging from 170 Å to 200 Å. When a small residue that appeared critical for packing was converted to leucine, it resulted in structural rearrangement to a helical polymer. Fluorescently tagged versions of the designed peptides form puncta in mammalian cells, which recover from photobleaching with markedly different kinetics. These structural folds could be potentially useful for directing in vivo protein assemblies with predetermined spacing and stabilities.

Alternate JournalNat Chem Biol
PubMed ID30061717
PubMed Central IDPMC6497057
Grant ListF32 GM125217 / GM / NIGMS NIH HHS / United States
R35 GM122603 / GM / NIGMS NIH HHS / United States