Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties
Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties
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DOI：
10.1080/07391102.2011.672632
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发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Fasano, Mauro
中科院分区：
文献类型：
--
作者：
Fanali, Gabriella;Ascenzi, Paolo;Fasano, Mauro
血清白蛋白（SA）是一种循环蛋白质，为许多内源性和外源性化合物提供了储存库和载体。至少有七个主要的结合位点已确定的结构和功能的调查，主要是在人类SA。SA在脊椎动物中是保守的，在蛋白质序列数据库中至少有49个条目。这组条目的多序列分析导致的定义的分支树的分子进化SA的直系同源物在脊椎动物中，从而显示所考虑的物种的聚类，与七鳃鳗SA（Lethenteron japonicum和Petromyzon marinus）在一个单独的外群。旨在寻找保守结构域的序列分析显示，大多数SA序列由三个重复结构域（约600个残基）组成，广泛表征为人类SA。相反，七鳃鳗SA是巨大的蛋白质（约1400个残基），包含7个重复结构域。SA家族的系统发育分析揭示了与序列数据库中物种的分类学分类的严格相关性。在SA中的配体结合位点的序列的集中检查显示，在所有站点中，参与配体结合的大多数残基是保守的，尽管对不同配体的通用性可能是高等生物特有的。此外，对不同位点之间分子联系的分析表明，变构调节机制可能仅限于高等脊椎动物。
Serum albumin (SA) is a circulating protein providing a depot and carrier for many endogenous and exogenous compounds. At least seven major binding sites have been identified by structural and functional investigations mainly in human SA. SA is conserved in vertebrates, with at least 49 entries in protein sequence databases. The multiple sequence analysis of this set of entries leads to the definition of a cladistic tree for the molecular evolution of SA orthologs in vertebrates, thus showing the clustering of the considered species, with lamprey SAs (Lethenteron japonicum and Petromyzon marinus) in a separate outgroup. Sequence analysis aimed at searching conserved domains revealed that most SA sequences are made up by three repeated domains (about 600 residues), as extensively characterized for human SA. On the contrary, lamprey SAs are giant proteins (about 1400 residues) comprising seven repeated domains. The phylogenetic analysis of the SA family reveals a stringent correlation with the taxonomic classification of the species available in sequence databases. A focused inspection of the sequences of ligand binding sites in SA revealed that in all sites most residues involved in ligand binding are conserved, although the versatility towards different ligands could be peculiar of higher organisms. Moreover, the analysis of molecular links between the different sites suggests that allosteric modulation mechanisms could be restricted to higher vertebrates.