Baker M E
Department of Medicine, University of California, San Diego, La Jolla.
Tumour Biol. 1988;9(2-3):123-36. doi: 10.1159/000217553.
Alpha-fetoprotein (AFP) and albumin are related proteins, which contain about 585 amino acid residues that are organized in a characteristic structure of 3 homologous domains of about 195 amino acid residues. We have compared the domains of mouse, rat, and human AFP and rat, bovine, and human albumin using computer programs designed to quantify relationships between proteins. The comparisons of corresponding domains of the AFPs (e.g. domain I of rat and human AFP) reveal that each domain is well conserved. Similar results were found for the comparisons of corresponding domains in the albumins. In contrast, there was much less similarity between corresponding domains of albumin and AFP. These comparisons between AFP and albumin revealed that: (1) the amino acid sequences in domain III, which is at their carboxy terminus, are most conserved, and (2) the amino acid sequences in domain I, which is at their amino terminus, are least conserved. This suggests that there are differences in the constraints on amino acid substitutions among the domains of AFP and albumin during the approximately 400 million years since they diverged from a common ancestor. Also, computer studies revealed that there are substantial differences between domains I, II, and III in each AFP and albumin species, which indicates that these domains are significantly different from their approximately 195 residue ancestral domain. Finally, we find that mouse and rat AFP are more dissimilar to the albumins than is human AFP. Overall, our computer analyses indicate that AFP and albumin can be considered to be composed of distinct, but related, approximately 195 residue proteins, each of which could differ in some of their properties; for example, the binding of fatty acids.
甲胎蛋白（AFP）和白蛋白是相关蛋白质，它们含有约585个氨基酸残基，这些氨基酸残基以约195个氨基酸残基的3个同源结构域的特征性结构排列。我们使用旨在量化蛋白质之间关系的计算机程序，比较了小鼠、大鼠和人类AFP以及大鼠、牛和人类白蛋白的结构域。对AFP相应结构域的比较（例如大鼠和人类AFP的结构域I）表明，每个结构域都高度保守。在白蛋白相应结构域的比较中也发现了类似结果。相比之下，白蛋白和AFP的相应结构域之间的相似性要小得多。AFP和白蛋白之间的这些比较表明：（1）位于其羧基末端的结构域III中的氨基酸序列最保守，（2）位于其氨基末端的结构域I中的氨基酸序列最不保守。这表明自它们从共同祖先分化以来的大约4亿年中，AFP和白蛋白各结构域对氨基酸替换的限制存在差异。此外，计算机研究表明，每种AFP和白蛋白物种的结构域I、II和III之间存在实质性差异，这表明这些结构域与其大约195个残基的祖先结构域有显著不同。最后，我们发现小鼠和大鼠的AFP与白蛋白的差异比人类AFP与白蛋白的差异更大。总体而言，我们的计算机分析表明，AFP和白蛋白可以被认为是由不同但相关的、大约195个残基的蛋白质组成，每种蛋白质在某些特性上可能有所不同；例如，脂肪酸的结合。
