Summary
Protein stability, expression, and resistance to proteolysis are often correlated. This is cited by (1). A community assessment of PROSS also found correlation between stability and expression (2). That has also been observed in antibodies, with lower expression levels and thermostabilities following Somatic hypermutation (3). The link between stability and resistance to proteolysis has been described by (4), (5), and (6).
Figures
Ref (4)
See also
- Stability-activity trade-off during enzyme design and evolution is highly local and not global
- Differences in thermostability of structurally similar proteins are due to differences in unfolding rates
1.
Teufl M, Zajc CU, Traxlmayr MW. Engineering Strategies to Overcome the Stability–Function Trade-Off in Proteins. ACS Synthetic Biology. 2022;11(3):1030–9. Available from: https://doi.org/10.1021/acssynbio.1c00512
2.
Peleg Y, Vincentelli R, Collins BM, Chen K-E, Livingstone EK, Weeratunga S, et al. Community-Wide Experimental Evaluation of the PROSS Stability-Design Method. Journal of Molecular Biology. 2021;433(13):166964. Available from: https://doi.org/10.1016/j.jmb.2021.166964
3.
Shehata L, Maurer DP, Wec AZ, Lilov A, Champney E, Sun T, et al. Affinity Maturation Enhances Antibody Specificity but Compromises Conformational Stability. Cell Reports. 2019;28(13):3300-3308.e4. Available from: https://doi.org/10.1016/j.celrep.2019.08.056
4.
Tzul FO, Vasilchuk D, Makhatadze GI. Evidence for the principle of minimal frustration in the evolution of protein folding landscapes. Proceedings of the National Academy of Sciences. 2017;114(9). Available from: https://doi.org/10.1073/pnas.1613892114
5.
Tsuboyama K, Dauparas J, Chen J, Laine E, Mohseni Behbahani Y, Weinstein JJ, et al. Mega-scale experimental analysis of protein folding stability in biology and design. Nature. 2023;620(7973):434–44. Available from: https://doi.org/10.1038/s41586-023-06328-6
6.
Diaz DJ, Gong C, Ouyang-Zhang J, Loy JM, Wells J, Yang D, et al. Stability Oracle: A Structure-Based Graph-Transformer for Identifying Stabilizing Mutations. openRxiv; 2023. Available from: https://doi.org/10.1101/2023.05.15.540857