Conservation of Salt Bridges in Protein Families

Abstract

A detailed computational analysis is presented that focuses on the relationship between structural attributes and the degree and mode of salt bridge conservation. A data set of conserved and non-conserved salt bridges was constructed from eight protein families, based on the structural alignment of family members. Salt bridges were defined at the secondary structure level rather than at the residue level, implying different possible modes of conservation: preservation (same charges at the same residue positions), compensation (reversal of charges), and complementation (maintenance of a salt bridge between two segments of secondary structures, not involving the same residue positions). Structural attributes such as the surface accessibility, distance from the active site, or type of secondary structures involved, were studied. No significant differences were found between conserved and non-conserved salt bridges, except for the surface accessibility. Conserved salt bridges were shown to be less exposed than non-conserved ones. Moreover, within the set of conserved salt bridges, the degree of conservation was shown to negatively correlate with surface exposure; however, not to an extent that could indicate a general role for electrostatic interactions in the protein interior. Examination of the most conserved salt bridge in each family showed a variety of typical features: Some involved the terminal segments of the protein, some were buried and one involved the catalytic site of the protein. Hence, the role of salt bridges is more specific, probably in fine tuning of a specific structure through the folding process or in determining the functional site. As for the conservation mode, preservations were found to predominate in the conserved interactions, while complementations were of secondary importance. Compensations occurred only rarely and mostly in exposed salt bridges, suggesting that this mechanism is not utilized frequently and especially not in important interactions.