Document Type
Article
Publication Date
2020
Keywords
Protein Stability, Intrinsically Disorder Propensity, Stable Mutant Proteins, Design of Disulfide Bond, Design of Protein Circular Permutant
Digital Object Identifier (DOI)
https://doi.org/10.3390/biom10010064
Abstract
Directed stabilization of globular proteins via substitution of a minimal number of amino acid residues is one of the most complicated experimental tasks. This work summarizes our research on the effect of amino acid substitutions on the protein stability utilizing the outputs of the analysis of intrinsic disorder predisposition of target proteins. This allowed us to formulate the basis of one of the possible approaches to the stabilization of globular proteins. The idea is quite simple. To stabilize a protein as a whole, one needs to find its "weakest spot" and stabilize it, but the question is how this weak spot can be found in a query protein. Our approach is based on the utilization of the computational tools for the per-residue evaluation of intrinsic disorder predisposition to search for the "weakest spot" of a query protein (i.e., the region(s) with the highest local predisposition for intrinsic disorder). When such "weakest spot" is found, it can be stabilized through a limited number of point mutations by introducing order-promoting residues at hot spots, thereby increasing structural stability of a protein as a whole. Using this approach, we were able to obtain stable mutant forms of several globular proteins, such as Gαo, GFP, ribosome protein L1, and circular permutant of apical domain of GroEL.
Rights Information
This work is licensed under a Creative Commons Attribution 4.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Biomolecules, v. 10, issue 1, art. 64
Scholar Commons Citation
Nagibina, Galina S.; Melnik, Bogdan S.; Uversky, Vladimir N.; Melnik, Tatiana N.; and Melnik, Bogdan S., "Intrinsic Disorder-based Design of Stable Globular Proteins" (2020). Molecular Medicine Faculty Publications. 829.
https://digitalcommons.usf.edu/mme_facpub/829
