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bioRxiv · 10.1101/2022.01.28.478135

A Chemical Mutagenesis Approach to Insert Post-Translational Modifications in Aggregation-Prone Proteins

Ge, Y.·Masoura, A.·Yang, J.·Aprile, F. A.
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Abstract

Neurodegenerative diseases are a class of disorders linked to the formation in the nervous system of fibrillar protein aggregates called amyloids. This aggregation process is affected by a variety of post-translational modifications, whose specific mechanisms are not fully understood yet. Emerging chemical mutagenesis technology is currently striving to address the challenge of introducing protein post-translational modifications, while maintaining proteins stable and soluble during the modification reaction. Several amyloidogenic proteins are highly aggregation-prone, and current modification procedures lead to unexpected precipitation of these proteins, affecting their yield and downstream characterization. Here, we present a method for maintaining amyloidogenic proteins soluble during chemical mutagenesis. As proof-of-principle, we applied our method to mimic the phosphorylation of the serine 26 and the acetylation of the lysine 28 of the 40-residue long variant of amyloid-{beta} peptide, whose aggregation is linked to Alzheimers disease.

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Ge, Y., Masoura, A., Yang, J., Aprile, F. A.. 2022-01-28. A Chemical Mutagenesis Approach to Insert Post-Translational Modifications in Aggregation-Prone Proteins. https://doi.org/10.1101/2022.01.28.478135

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