National Institute for Biostructures and Biosystems, Roma, Italy.
IUBMB Life. 2013 Jun;65(6):544-9. doi: 10.1002/iub.1164. Epub 2013 Apr 9.
Serum albumin, α-fetoprotein, afamin (also named α-albumin and vitamin E binding protein), and vitamin D binding protein are members of the albuminoid superfamily. Albuminoids are plasma proteins characterized by a marked ability for ligand binding and transport. Here, a focused phylogenetic analysis of sequence evolution by maximum likelihood of fatty acid binding sites FA1-FA7 of mammalian albuminoids reveals that the FA1, FA2, and FA3+FA4 sites in serum albumins have evolved from the most recent common ancestor through an intermediate that has originated the α-fetoprotein and afamin clades. The same topology has been observed for the whole protein sequences, for the sequences of all the fatty acid binding sites (FA1-FA7) taken together, and for the allosteric core corresponding to residues 1-303 of human serum albumin. The quantitative divergence analysis indicates that the ligand binding cleft corresponding to the FA2 site could be the main determinant of allosteric properties of serum albumins only. In fact, this binding cleft is structurally not effective in vitamin D binding proteins, whereas key residues that serve to allocate the allosteric effectors are not present in afamins and α-fetoproteins.
血清白蛋白、甲胎蛋白、胎球蛋白（也称为α-白蛋白和维生素 E 结合蛋白）和维生素 D 结合蛋白是白蛋白超家族的成员。白蛋白超家族的特点是具有显著的配体结合和运输能力。在这里，通过最大似然法对哺乳动物白蛋白的脂肪酸结合位点 FA1-FA7 的序列进化进行了集中的系统发育分析，结果表明血清白蛋白中的 FA1、FA2 和 FA3+FA4 位点是从最近的共同祖先通过一个中间祖先进化而来的，这个中间祖先起源于甲胎蛋白和胎球蛋白分支。同样的拓扑结构也出现在整个蛋白质序列、所有脂肪酸结合位点（FA1-FA7）的序列以及人血清白蛋白中对应于残基 1-303 的变构核心中。定量分歧分析表明，对应于 FA2 位点的配体结合裂隙可能是血清白蛋白变构性质的主要决定因素。事实上，这个结合裂隙在维生素 D 结合蛋白中在结构上是无效的，而在胎球蛋白和甲胎蛋白中不存在分配变构效应物的关键残基。
