Kinetics of Peptide Aggregation

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Virginia Tech


The most thermodynamically stable biological structure is the cross-beta secondary structure of the "amyloid"or "prion". As a testament to its stability, the amyloid occurs naturally in 2 rare instances: as a mechanism to protect or destroy life. Pathogenic amyloids are the signature of neurological disorders such as Alzheimer's and Parkinson's disease and bovine spongiform encephalopathy (BSE), which have no effective treatments or known cures. Pathogenic amyloids appear as nanometer sized "plaques" that self-assemble over time. The plaques usually are well-organized crystalline/fibrous structures ~10-20 nm in diameter and >100 nm long. "Functional" amyloids are very rare in nature and serve the direct purpose to proliferate life. Stalks to protect eggs, fibers to coat spores, and adhesive proteins of bacteria, algae, fungi, and mollusks are examples. Functional amyloids can be larger than pathogenic amyloids by 1-2 orders of magnitude.

There is a burgeoning research field based on emulating the amyloid. This is because it can be formed from a host of proteins or peptides simply by denaturing them enough to form a cross-beta secondary structure and has a modulus of >10 GPa. As a general reference, "protein" is usually a very high molecular weight, naturally occurring molecule and "peptide" is a much smaller portion of a natural protein or a non-natural molecule synthesized from a few amino acids. Researchers are increasingly attempting to take advantage of the functional amyloid. It is still not understood how the functional amyloid self-assembles or why it can be larger than the pathogenic amyloid. We have identified a potential pathway to large functional amyloids that involves a long alpha-helix containing protein (the "adder") undergoing an alpha to beta transition in the presence of a hydrophobic beta-sheet template. Testing our hypothesis against proteins found in natural large functional amyloids seems to suggest it is a ubiquitous process. The resulting material is a fiber composite similar to the native structures.



protein aggregation, cross-beta, peptide, amyloids, kinetics