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bioRxiv · 10.1101/2021.05.09.443347

Can charge-reversal be considered as a strategy for attaining thermal stability in proteins?

Hait, S.·Basu, S.·Kundu, S.
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Abstract

Do charge reversal mutations (CRM) naturally occur in mesophilic-thermophilic/hyperthermophilic (M-T/HT) orthologous proteins? Do they contribute to thermal stability by altering charge-charge interactions? A careful investigation on 1550 M-T/HT orthologous protein pairs with remarkable structural and topological similarity extracts the role of buried and partially exposed CRMs in enhancing thermal stability. Our findings could assist in engineering thermo-stable variants of proteins. SIGNIFICANCEProtein engineering is one of the hot topics for decades specifically for its applications in different fields like de-novo protein design, directed evolution, making highly stable variants for food and drug industry etc. Proteins from organisms living in extreme environments are therefore a matter of common interest for scientists from different disciplines. Over three decades of study has already found several sequence and structural adaptations related to thermal stability, while charge reversal study remains ignored to a large extent. Influenced by natures strategy, our study provides a systemic understanding of how proper designing of few partially exposed and buried CRMs significantly contributes to thermal stability by altering the short distance electrostatic interactions.

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Hait, S., Basu, S., Kundu, S.. 2021-05-10. Can charge-reversal be considered as a strategy for attaining thermal stability in proteins?. https://doi.org/10.1101/2021.05.09.443347

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