Schueler O, Margalit H
Department of Molecular Genetics, Hebrew University Hadassah Medical School, Jerusalem, Israel.
J Mol Biol. 1995 Apr 21;248(1):125-35. doi: 10.1006/jmbi.1995.0206.
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.
本文进行了详细的计算分析，重点关注结构属性与盐桥保守程度及保守模式之间的关系。基于家族成员的结构比对，从八个蛋白质家族构建了保守和非保守盐桥的数据集。盐桥在二级结构水平而非残基水平上定义，这意味着存在不同的保守模式：保留（相同残基位置具有相同电荷）、补偿（电荷反转）和互补（二级结构的两个片段之间维持盐桥，不涉及相同残基位置）。研究了诸如表面可及性、与活性位点的距离或所涉及的二级结构类型等结构属性。除了表面可及性外，保守和非保守盐桥之间未发现显著差异。结果表明，保守盐桥比非保守盐桥暴露程度更低。此外，在保守盐桥集合中，保守程度与表面暴露呈负相关；然而，这种相关性的程度并不足以表明静电相互作用在蛋白质内部具有普遍作用。对每个家族中最保守的盐桥进行检查发现了各种典型特征：一些涉及蛋白质的末端片段，一些被掩埋，还有一个涉及蛋白质的催化位点。因此盐桥的作用更具特异性，可能是在折叠过程中对特定结构进行微调或确定功能位点。至于保守模式，保留在保守相互作用中占主导地位，而互补则次要。补偿很少发生，且大多发生在暴露的盐桥中，这表明这种机制不常被利用，尤其是在重要相互作用中。
