Zhang’s De novo cross-α amyloid peptide paper published in Nature Chemical Biology


Post-doc Shao-Qing Zhang's work on design of alpha-helical peptides that resemble the organization of amyloid plaques in the brain was published recently in Nature Chemical Biology. This work follows recent work in the journal Science expanding upon a recently discovery of toxic secreted bacterial peptide found in nature in biofilms that induces cytotoxicity via formation of alpha-helical fibrils. Here, Zhang and co-workers take a structural approach to understand the design principles at the heart of these spiraling cross-alpha amyloid-like assemblies by making them from novel synthetic peptides!

rendering diagram

Ultimately, they were able to design a series of peptides that form fibrils, as seen by electron microscopy, that bind to amyloid-binding dyes. The unique supermolecular architecture of most of these peptides were revealed in high resolution by X-ray diffraction. In this way, it was clear that the molecular packing interactions at certain amino acids between each adjacent peptide in the fiber translate to the geometry and morphology of the fiber in a tunable manner.

Interestingly, FRAP experiments in cells show that in vivo the fibrils are not fluid, that is the peptides in each assembly act as fixed polymers rather than rapidly assembling and disassembling. These are the first assemblies of this kind, not yet observed in nature, and these peptides should be useful tools in nanotechnology or ordering biological material into programmable arrays in cells.


This work was done in collaboration with the UCSF Shu lab.