Why does the structure for cellular retinol binding protein show interactions with cadmium ions? A structure of cellular retinol binding protein (1CRB) contains two cadmium ions as ligands. Is Cd2+ a ligand of CRBP and, if so, is that interaction necessary for protein function or is the protein a transporter to remove cadmium? My other thought is that the interaction only appears as a result of the methods the scientists used to determine the structure of the protein.

As far as I am aware, there is no known requirement for Cd in mammalian systems, but it is extremely toxic (Waalkes & Goering).

It would seem that cadmium is required to get crystals of RBP, and its presence is an artifact of the crystallization process (ref):

> Pig holoRBP crystals were obtained at 277 K by the sitting-drop vapor- diffusion method, at a final protein concentration of approximately 8 mg ml ~ and in the presence of 8%(v/v) 2-methyl-2,4- pentanediol, 3mM cadmium acetate, 0.1 M Tris-acetate, pH = 6.8

The only mammalian Cd-binding protein I am aware of is metallothione (ref), which was originally isolated as a Cd-binding protein (ref), and allows safe transport of a highly toxic metal.

Carbonic anhydrase from the marine diatom _Thalassiosira weissflogi_ can use Cd as active-site metal (typically when Zn is low) and this may explain "the nutrient-like behaviour of cadmium in the ocean" [ref and ref]