Molecular phylogenetic analyses of albuminoids reveal the molecular evolution of allosteric properties

Abstract

Serum albumin, a-fetoprotein, afamin (also named a-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 FA31FA4 sites in serum albumins have evolved from the most recent common ancestor through an intermediate that has originated the a-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 a-fetoproteins.

Albuminoid Genes: Evolving at the Interface of Dispensability and Selection

“…Therefore, albuminoid proteins are involved in central homeostatic functions. Although albumin is one of the most extensively investigated proteins, few studies have analyzed its evolutionary history, and most of these mainly aimed at reconstructing the duplication/divergence events that originated the four family member genes ( Gibbs et al 1998 ; Ascenzi et al 2013 ). Herein, we analyzed the evolutionary history of albuminoid genes at inter- and intraspecific levels.…”

Serum albumin and nucleic acids biodistribution: From molecular aspects to biotechnological applications

“…the organism's complexity and the exposure to environmental factors. 2,8,42,93 Human SA (HSA) is the most abundant plasma protein (the serum concentration ranging between 35 and 50 g/L) and represents the main carrier of fatty acids (FAs) as well as of a wide range of endogenous and exogenous compounds, thus improving their solubility and half-life. 40,99 HSA also regulates the oncotic pressure and the fluid distribution between the body compartments, possibly providing the modification of ligands, rendering potential toxins harmless, affecting the pharmacokinetics of many drugs, and displaying anti-oxidant and (pseudo-) enzymatic properties.…”

“…SA is one of the most evolutionarily changeable proteins, the number of ligand binding domains changing from seven in lamprey to three in humans. These differences possibly reflect both the organism's complexity and the exposure to environmental factors 2,8,42,93 …”