Abstract
BackgroundThe hydrogen bond patterns between mainchain atoms in protein structures not only give rise to regular secondary structures but also satisfy mainchain hydrogen bond potential. However, not all mainchain atoms can be satisfied through hydrogen bond interactions that arise in regular secondary structures; in some locations sidechain-to-mainchain hydrogen bonds are required to provide polar group satisfaction. Buried polar residues that are hydrogen-bonded to mainchain amide atoms tend to be highly conserved within protein families, confirming that mainchain architecture is a critical restraint on the evolution of proteins. We have investigated the stabilizing roles of buried polar sidechains on the backbones of protein structures by performing an analysis of solvent inaccessible residues that are entirely conserved within protein families and superfamilies and hydrogen bonded to an equivalent mainchain atom in each family member.ResultsWe show that polar and sometimes charged sidechains form hydrogen bonds to mainchain atoms in the cores of proteins in a manner that has been conserved in evolution. Although particular motifs have previously been identified where buried polar residues have conserved roles in stabilizing protein structure, for example in helix capping, we demonstrate that such interactions occur in a range of architectures and highlight those polar amino acid types that fulfil these roles. We show that these buried polar residues often span elements of secondary structure and provide stabilizing interactions of the overall protein architecture.ConclusionsConservation of buried polar residues and the hydrogen-bond interactions that they form implies an important role for maintaining protein structure, contributing strong restraints on amino acid substitutions during divergent protein evolution. Our analysis sheds light on the important stabilizing roles of these residues in protein architecture and provides further insight into factors influencing the evolution of protein families and superfamilies.
Highlights
The hydrogen bond patterns between mainchain atoms in protein structures give rise to regular secondary structures and satisfy mainchain hydrogen bond potential
What are the features of sidechain-to-mainchain hydrogen bonds formed by polar sidechains? Which amino acids are involved? What kinds of structures do these buried polar residues maintain? Are they local to a secondary structure or do they link between different helices and strands, stabilizing tertiary structure? In this report we focus purely on buried polar residues that are entirely conserved within protein families and superfamilies, hydrogen bonding to a mainchain atom in each family member
We have previously demonstrated that buried polar residues, small in number, tend to be more conserved when their hydrogen-bonding potential is satisfied or where they form hydrogen bonds to mainchain atoms [21]
Summary
The hydrogen bond patterns between mainchain atoms in protein structures give rise to regular secondary structures and satisfy mainchain hydrogen bond potential. As Pauling and Corey realised, satisfaction of hydrogen bonding potential of polypeptide mainchain functions is one of the major factors that give rise to the β-strand and α-helix [1,2] These regular elements of secondary structure give their names to the main features of protein structure: classical β-sheets, α-helical bundles, αβ-Rossman fold, αβ-barrel and many others. In this report we focus purely on buried polar residues that are entirely conserved within protein families and superfamilies, hydrogen bonding to a mainchain atom in each family member We hypothesise that such buried sidechain-to-mainchain hydrogen bonds satisfy mainchain hydrogen bonding potential where secondary structures cannot be formed, and in so doing become irreplaceable elements of the overall architecture. Some are joists or braces, spanning the helices and strands, while others form truss-like structures that support complex loop structures (Figure 2)
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