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bioRxiv · 10.1101/323030

Cooperative induction of ordered peptide and fatty acid aggregates

Riek, R.·Greenwald, J.·Kwiatkowski, W.·Bomba, R.
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Abstract

Interactions between biological membranes and disease-associated amyloids are well documented and their prevalence suggests that an inherent affinity exists between these two distinct molecular assemblies. Within the framework of our research project on amyloids and the origins of life, we hypothesized here that such interactions could increase both the sequence and structure space of peptide amyloids in a heterogeneous system and that if cooperative in nature, the interaction could be advantageous to the propagation of these entities in a prebiotic context. Thus, we have investigated the interplay between vesicle-forming fatty acids and amyloidogenic peptides, the respective precursors of lipids and proteins. Individually they are able to form ordered structures under a limited range of conditions with the bilayer of fatty acid vesicles and the cross-{beta} core of amyloids both being repetitive structures that could in principle support a cooperative interaction. Here we report that an 8-residue basic peptide that can form an amphipathic {beta}-strand, that is soluble at neutral pH and that can form amyloids above its pI at pH 11, is also able to cooperatively form novel co-aggregates of diverse structure with and in the context of simple fatty acids at neutral pH. Below the critical vesicle concentration (CVC) the mixtures of fatty acid and peptide yield a flocculent precipitate with an underlying {beta}-structure. Above the CVC, the mixtures yield ribbon or tube-like structures that bear some of the hallmarks of amyloids yet have associated with them a significant amount of fatty acids, likely in a bilayer structure. In the context of the origin of cellular life these results expand the phase space of both peptides and fatty acids while providing a simple yet robust physical connection between two distinct biological entities relevant for life.

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Riek, R., Greenwald, J., Kwiatkowski, W., Bomba, R.. 2018-05-28. Cooperative induction of ordered peptide and fatty acid aggregates. https://doi.org/10.1101/323030

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