Shionyu M, Takahashi K, Gō M
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8602, Japan.
J Mol Evol. 2001 Oct-Nov;53(4-5):416-29. doi: 10.1007/s002390010231.
Tertiary structures of proteins are conserved better than their primary structures during evolution. Quaternary structures or subunit organizations, however, are not always conserved. A typical case is found in hemoglobin family. Although human, Scapharca, and Urechis have tetrameric hemoglobins, their subunit contacts are completely different from each other. We report here that only one or two amino acid replacements are enough to create a new contact between subunits. Such a small number of chance replacements is expected during the evolution of hemoglobins. This result explains why different modes of subunit interaction evolved in animal hemoglobins. In contrast, certain interactions between subunits are necessary for cooperative oxygen binding. Cooperative oxygen binding is observed often in dimeric and tetrameric hemoglobins. Conformational change of a subunit induced by the first oxygen binding to the heme group is transmitted through the subunit contacts and increases the affinity of the second oxygen. The tetrameric hemoglobins from humans and Scapharca have cooperativity in spite of their different modes of subunit contact, but the one from Urechis does not. The relationship between cooperativity and the mode of subunit contacts is not clear. We compared the atomic interactions at the subunit contact surface of cooperative and non-cooperative tetrameric hemoglobins. We show that heme-contact modules M3-M6 play a key role in the subunit contacts responsible for cooperativity. A module was defined as a contiguous peptide segment having compact conformation and its average length is about 15 amino acid residues. We show that the cooperative hemoglobins have interactins involving at least two pairs of modules among the four heme-contact modules at subunit contact.
在进化过程中，蛋白质的三级结构比其一级结构保存得更好。然而，四级结构或亚基组织并不总是保守的。血红蛋白家族就是一个典型的例子。虽然人类、蚶和星虫都有四聚体血红蛋白，但它们的亚基接触方式却完全不同。我们在此报告，只需一两个氨基酸替换就足以在亚基之间形成新的接触。在血红蛋白的进化过程中，预期会出现如此少量的偶然替换。这一结果解释了动物血红蛋白中亚基相互作用的不同模式是如何进化的。相反，亚基之间的某些相互作用对于协同氧结合是必要的。协同氧结合在二聚体和四聚体血红蛋白中经常观察到。第一个氧与血红素基团结合诱导的亚基构象变化通过亚基接触传递，并增加了第二个氧的亲和力。人类和蚶的四聚体血红蛋白尽管亚基接触模式不同，但都具有协同性，而星虫的四聚体血红蛋白则没有。协同性与亚基接触模式之间的关系尚不清楚。我们比较了协同和非协同四聚体血红蛋白亚基接触表面的原子相互作用。我们发现血红素接触模块M3 - M6在负责协同性的亚基接触中起关键作用。一个模块被定义为具有紧密构象的连续肽段，其平均长度约为15个氨基酸残基。我们表明，协同血红蛋白在亚基接触处的四个血红素接触模块中至少有两对模块参与相互作用。
