On the evolutionary conservation of hydrogen bonds made by buried polar amino acids: the hidden joists, braces and trusses of protein architecture
On the evolutionary conservation of hydrogen bonds made by buried polar amino acids: the hidden joists, braces and trusses of protein architecture
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关于埋藏极性氨基酸形成的氢键的进化守恒：蛋白质结构的隐藏托梁、支撑和桁架
DOI：
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发表时间：
2010
影响因子：
3.4
通讯作者：
T. Blundell
中科院分区：
文献类型：
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作者：
Catherine L. Worth;T. Blundell
蛋白质结构中主链原子间的氢键模式不仅能形成规则的二级结构，而且满足主链氢键电位。然而，并不是所有的主链原子都可以通过在规则二级结构中出现的氢键相互作用来满足；在某些位置，侧链到主链的氢键需要提供极性基团满足。与主链酰胺原子氢键结合的埋藏极性残基往往在蛋白质家族中高度保守，证实主链结构是蛋白质进化的关键制约因素。我们通过分析在蛋白质家族和超家族中完全保守的溶剂不可接近残基，以及在每个家族成员中与等效主链原子成键的氢键，研究了埋藏的极性侧链在蛋白质结构骨架上的稳定作用。结果：我们发现极性侧链和有时带电的侧链以一种在进化中保守的方式与蛋白质核心的主链原子形成氢键。虽然之前已经确定了特定的基序，其中埋藏的极性残基在稳定蛋白质结构中具有保守作用，例如在螺旋盖层中，但我们证明了这种相互作用发生在一系列结构中，并强调了那些发挥这些作用的极性氨基酸类型。我们发现这些埋藏的极性残基通常跨越二级结构的元素，并提供稳定的整体蛋白质结构相互作用。结论埋藏极性残基的保存及其形成的氢键相互作用对维持蛋白质结构具有重要作用，在蛋白质分化进化过程中对氨基酸取代有很强的限制。我们的分析揭示了这些残基在蛋白质结构中的重要稳定作用，并为影响蛋白质家族和超家族进化的因素提供了进一步的见解。
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.
影响因子：
56.9
作者：
PRESTA, LG;ROSE, GD
通讯作者：
ROSE, GD