Plasma retinol-binding protein: structure and interactions with retinol, retinoids, and transthyretin.
Retinol-binding protein (RBP) is the retinol-specific transport protein present in plasma. The available crystal structures of different forms of RBP have provided details of the interactions of this binding protein with retinol, retinoids, and transthyretin (TTR, one of the plasma carriers of thyroid hormones). The core of RBP is a beta-barrel, the cavity of which accommodates retinol, establishing with its buried portions apolar contacts. Instead, the retinol hydroxyl is near the protein surface, in the region of the entrance loops surrounding the opening of the binding cavity, and participates in polar interactions. The stability of the retinol-RBP complex appears to be further enhanced when holo-RBP is bound to TTR. Accordingly, the region of the entrance loops represents the contact area of RBP interacting with the TTR counterpart, such that the hydroxyl of the RBP-bound vitamin becomes fully buried in the holo-RBP-TTR complex. Limited protein conformational changes affecting the entrance loops, which lead to a decrease or loss of the binding affinity of RBP for TTR, have been demonstrated for apo-RBP and RBP in complex with retinoids modified in the area of the retinol hydroxyl. A relatively small number of amino acid residues of RBP, essentially confined to the region of the entrance loops, and of TTR appear to play a critical role in the formation of the RBP-TTR complex, as established by crystallographic studies, mutational analysis, and amino acid sequence analysis of phylogenetically distant RBPs and TTRs. Overall, the available evidence indicates the existence of a high degree of complementarity between RBP and TTR, the contact areas of which are highly sensitive to conformational changes and amino acid replacements.
Zanotti
Giuseppe
G
Department of Organic Chemistry, University of Padova, 35131 Padua, Italy.
Berni
Rodolfo
R
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D011228:Prealbumin / Q000737:chemistry* / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D054839:Retinol-Binding Proteins, Plasma; D016415:Sequence Alignment; D014801:Vitamin A / Q000737:chemistry* / Q000378:metabolism*
D011228:Prealbumin; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A