Lipocalins are 15–30 kDa extracellular proteins that contain a lipocalin motif comprising an N-terminal 310-like helix, an eight-stranded continuously hydrogen-bonded antiparallel β-barrel, and a C-terminal α-helix [1]. Lipocalins are present in a wide range of species, from nematodes to mammals. Lipocalins bind to hydrophobic substances through their lipocalin motifs and play important roles in the physiological functions of the bound substances. For example, retinol binding protein 4, a lipocalin found in mammals, binds to retinol or retinoic acid (vitamin A metabolites: retinoids) and facilitates retinoids transport [2]. Major urinary proteins, a subfamily of lipocalins predominantly found in rodent urine and secretions, contribute to the induction of sexual behavior by binding to pheromones [[3], [4], [5], [6], [7]]. Tributyltin (TBT)-binding proteins (TBT-bps), a family of lipocalins found in a wide range of fish species, bind to the marine pollutant TBT, which have been concerned as an endocrine-disrupting chemical, to reduce its toxicity [[8], [9], [10], [11]].

Complement component 8 (C8) consists of three non-identical subunits (α, β, and γ), and the C8γ subunit is linked to the C8α subunit via a disulfide bond formed between their respective cysteine residues [[12], [13], [14]]. Although C8 proteins are the components of the membrane attack complex (MAC; C5b6789), which exhibits bacteriolysis by puncturing the cell walls of bacteria, C8γ is not necessary for the function of MAC [15]. Specific details of the functions of C8γ within the complement immune system are poorly understood, but C8γ is the only complement component subunit that contains a lipocalin motif, indicating that C8γ may act as a carrier protein for endogenous or exogenous chemicals and that it is possibly involved in various physiological functions of endogenous ligands or the toxicological effects of exogenous chemicals. Indeed, an X-ray crystallographic study has revealed that lauric acid (LA) binds to the lipocalin pocket of human C8γ (hC8γ) [16]. In addition, we have previously reported that tri-substituted organotin compounds such as triphenyltin (TPT) and TBT bind to specific sites of mouse C8γ (mC8γ) [17]. However, little is known about the species differences in its chemical binding properties between humans and mice.

Here, we examined the chemical binding properties of both hC8γ and mC8γ by means of a radioligand binding assay and found that [14C]TPT binds to hC8γ. Analyses with several other group 14 compounds revealed that the compounds must have substituents of an appropriate bulkiness and a central metal atom to allow them to bind to hC8γ and mC8γ. Together, the present results shed light on the function of C8γ in possibly altering the physiological or toxicological actions of group 14 metal compounds with tributyl or triphenyl substituents in humans and mice.