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Research Seminar: 1. Structural hot spots for the solubility of globular proteins, and 2. Targeted Protein aggregation by synthetic amyloids

28 February 2018

Dr. Frederic Rousseau & Dr. Joost Schymkowitz, VIB-KU Leuven Center for Brain & Disease Research, Department of Cellular and Molecular Medicine, KU Leuven, Belgium

Tuesday 6th March, 1.00 p.m., Stacey Lecture Theatre 1


Joost SchymkowitzStructural hot spots for the solubility of globular proteins

Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human a-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function.

Frederic RousseauTargeted Protein aggregation by synthetic amyloids

We have recently designed a number of synthetic amyloid that exploiting the sequence specificity of amyloid-like aggregation to induce targeted functional knockdown of proteins. I will discuss how we used this approach to generate beneficial plant phenotypes but also antitumoral and antibacterial amyloid peptides.

Finally I will discuss the possible implication of these findings for the mechanism of toxicity of amyloid in disease.



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