Structural and functional restraints in the evolution of protein families and superfamilies

Abstract

Divergent evolution of proteins reflects both selectively advantageous and neutral amino acid substitutions. In the present article, we examine restraints on sequence, which arise from selectively advantageous roles for structure and function and which lead to the conservation of local sequences and structures in families and superfamilies. We analyse structurally aligned members of protein families and superfamilies in order to investigate the importance of the local structural environment of amino acid residues in the acceptance of amino acid substitutions during protein evolution. We show that solvent accessibility is the most important determinant, followed by the existence of hydrogen bonds from the side-chain to main-chain functions and the nature of the element of secondary structure to which the amino acid contributes. Polar side chains whose hydrogen-bonding potential is satisfied tend to be more conserved than their unsatisfied or non-hydrogen-bonded counterparts, and buried and satisfied polar residues tend to be significantly more conserved than buried hydrophobic residues. Finally, we discuss the importance of functional restraints in the form of interactions of proteins with other macromolecules in assemblies or with substrates, ligands or allosteric regulators. We show that residues involved in such functional interactions are significantly more conserved and have differing amino acid substitution patterns.

On nucleotide solvent accessibility in RNA structure

“…One of the prospective ways to reveal these relations is an analysis of 3-dimensional structures of RNA and RNA-protein complexes. This approach has been successfully used for analysis of conformational features of interacting surfaces in proteins (e.g., (Gong et al, 2009)). …”

The fine details of evolution

“…Over the last half century, studies of the three-dimensional structures of proteins have revealed how a protein's three-dimensional structure relates to its biochemical function. Gong et al [16] show how different locations in the three-dimensional structure impose different constraints on which amino acid substitutions can be tolerated in order to preserve structure and/or function (see pp. 727-733).…”

The Ubiquity of the Insulin Superfamily Across the Eukaryotes Detected Using a Bioinformatics Approach

“…Interestingly, the 16th residue, which corresponds to a small aminoacid, is occupied in mammalian insulins by a glycine, with a positive main-chain torsion angle that allows the chain to change direction sharply. On the other hand, the positions involved in dimer formation are occupied by hydrophobic residues in all species except the hystricomorphs (Gong et al, 2009).…”