Summary
Protein dynamics are inversely related to specificity (1).
Details
Examples provided by (1)
- Conformational entropy in antibodies is inversely proportional to antigen affinity
- (Ubiquitin) adopts an ensemble of conformations (detected using (NMR)) that contains representatives closely aligning with snapshots of bound structures
- T-cell receptors adopt multiple conformations in unbound states
- Cytochrome P450 2A6 is not flexible and has narrow affinity, whereas 3A4 is flexible and has wide affinity
- SEPALLATA3 variants with more prolines being more specific than those without(2)
This also has ramifications for the evolution of new functions, which are predicted by the authors to arise from a subset of representatives of the conformational ensemble.
1.
Tokuriki N, Tawfik DS. Protein Dynamism and Evolvability. Science. 2009;324(5924):203–7. Available from: https://doi.org/10.1126/science.1169375
2.
Alhindi T, Zhang Z, Ruelens P, Coenen H, Degroote H, Iraci N, et al. Protein interaction evolution from promiscuity to specificity with reduced flexibility in an increasingly complex network. Scientific Reports. 2017 Mar;7(1). Available from: http://dx.doi.org/10.1038/srep44948