Design of stable circular permutants of the GroEL chaperone apical domain

Design of stable circular permutants of the GroEL chaperone apical domain

Enhancing protein stability holds paramount significance in biotechnology, therapeutics, and the food industry. Circular permutations offer a distinctive avenue for manipulating protein stability while keeping intra-protein interactions intact. Amidst the creation of circular permutants, determining...

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Bibliographic Details
Published in:Cell communication and signaling Vol. 22; no. 1; p. 90
Main Authors: Melnik, Tatiana N, Majorina, Maria A, Vorobeva, Daria E, Nagibina, Galina S, Veselova, Victoria R, Glukhova, Ksenia A, Pak, Marina A, Ivankov, Dmitry N, Uversky, Vladimir N, Melnik, Bogdan S
Format: Journal Article
Language:English
Published: England BioMed Central 01-02-2024
BMC
Subjects:
Amino acids
Biotechnology
Circular dichroism
Design
Food industry
Heat
Hypotheses
Protein interaction
Proteins
Spectrum analysis
Temperature
Vectors (Biology)
Japan
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Summary:Enhancing protein stability holds paramount significance in biotechnology, therapeutics, and the food industry. Circular permutations offer a distinctive avenue for manipulating protein stability while keeping intra-protein interactions intact. Amidst the creation of circular permutants, determining the optimal placement of the new N- and C-termini stands as a pivotal, albeit largely unexplored, endeavor. In this study, we employed PONDR-FIT's predictions of disorder propensity to guide the design of circular permutants for the GroEL apical domain (residues 191-345). Our underlying hypothesis posited that a higher predicted disorder value would correspond to reduced stability in the circular permutants, owing to the increased likelihood of fluctuations in the novel N- and C-termini. To substantiate this hypothesis, we engineered six circular permutants, positioning glycines within the loops as locations for the new N- and C-termini. We demonstrated the validity of our hypothesis along the set of the designed circular permutants, as supported by measurements of melting temperatures by circular dichroism and differential scanning microcalorimetry. Consequently, we propose a novel computational methodology that rationalizes the design of circular permutants with projected stability. Video Abstract.
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ISSN:1478-811X
1478-811X
DOI:10.1186/s12964-023-01426-4