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- Title
Protein conformational diversity modulates sequence divergence.
- Authors
Juritz, Ezequiel; Palopoli, Nicolas; Fornasari, Maria Silvina; Fernandez-Alberti, Sebastian; Parisi, Gustavo
- Abstract
It is well established that the conservation of protein structure during evolution constrains sequence divergence. The conservation of certain physicochemical environments to preserve protein folds and then the biological function originates a site-specific structurally constrained substitution pattern. However, protein native structure is not unique. It is known that the native state is better described by an ensemble of conformers in a dynamic equilibrium. In this work, we studied the influence of conformational diversity in sequence divergence and protein evolution. For this purpose, we derived a set of 900 proteins with different degrees of conformational diversity from the PCDB database, a conformer database. With the aid of a structurally constrained protein evolutionary model, we explored the influence of the different conformations on sequence divergence. We found that the presence of conformational diversity strongly modulates the substitution pattern. Although the conformers share several of the structurally constrained sites, 30% of them are conformer specific. Also, we found that in 76% of the proteins studied, a single conformer outperforms the others in the prediction of sequence divergence. It is interesting to note that this conformer is usually the one that binds ligands participating in the biological function of the protein. The existence of a conformer-specific site-substitution pattern indicates that conformational diversity could play a central role in modulating protein evolution. Furthermore, our findings suggest that new evolutionary models and bioinformatics tools should be developed taking into account this substitution bias.
- Publication
Molecular biology and evolution, 2013, Vol 30, Issue 1, p79
- ISSN
1537-1719
- Publication type
Journal Article
- DOI
10.1093/molbev/mss080