Balaji S, Aruna S, Srinivasan N
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Proteins. 2003 Dec 1;53(4):783-91. doi: 10.1002/prot.10416.
Occurrence and accommodation of charged amino acid residues in proteins that are structurally equivalent to buried non-polar residues in homologues have been investigated. Using a dataset of 1,852 homologous pairs of crystal structures of proteins available at 2A or better resolution, 14,024 examples of apolar residues in the structurally conserved regions replaced by charged residues in homologues have been identified. Out of 2,530 cases of buried apolar residues, 1,677 of the equivalent charged residues in homologues are exposed and the rest of the charged residues are buried. These drastic substitutions are most often observed in homologous protein pairs with low sequence identity (<30%) and in large protein domains (>300 residues). Such buried charged residues in the large proteins are often located in the interface of sub-domains or in the interface of structural repeats, Beyond 7A of residue depth of buried apolar residues, or less than 4% of solvent accessibility, almost all the substituting charged residues are buried. It is also observed that acidic sidechains have higher preference to get buried than the positively charged residues. There is a preference for buried charged residues to get accommodated in the interior by forming hydrogen bonds with another sidechain than the main chain. The sidechains interacting with a buried charged residue are most often located in the structurally conserved regions of the alignment. About 50% of the observations involving hydrogen bond between buried charged sidechain and another sidechain correspond to salt bridges. Among the buried charged residues interacting with the main chain, positively charged sidechains form hydrogen bonds commonly with main chain carbonyls while the negatively charged residues are accommodated by hydrogen bonding with the main chain amides. These carbonyls and amides are usually located in the loops that are structurally variable among homologous proteins.
对蛋白质中带电荷氨基酸残基的出现情况及其与同源物中被掩埋的非极性残基在结构上的等效性进行了研究。利用一组分辨率为2埃或更高的1852对蛋白质晶体结构同源对数据集，已鉴定出14024个结构保守区域中被同源物中的带电荷残基取代的非极性残基实例。在2530个被掩埋的非极性残基案例中，同源物中1677个等效的带电荷残基是暴露的，其余带电荷残基则被掩埋。这些剧烈的取代最常出现在序列同一性较低（<30%）的同源蛋白质对以及大的蛋白质结构域（>300个残基）中。大蛋白质中此类被掩埋的带电荷残基通常位于子结构域的界面或结构重复的界面处。在被掩埋的非极性残基深度超过7埃或溶剂可及性小于4%的情况下，几乎所有取代的带电荷残基都是被掩埋的。还观察到酸性侧链比带正电荷的残基更倾向于被掩埋。被掩埋的带电荷残基更倾向于通过与另一个侧链而非主链形成氢键来容纳在内部。与被掩埋的带电荷残基相互作用的侧链最常位于比对的结构保守区域。涉及被掩埋的带电荷侧链与另一个侧链之间氢键的观察结果中，约50%对应于盐桥。在与主链相互作用的被掩埋带电荷残基中，带正电荷的侧链通常与主链羰基形成氢键，而带负电荷的残基则通过与主链酰胺形成氢键来容纳。这些羰基和酰胺通常位于同源蛋白质中结构可变的环中。
