Recognition mechanism of galectin-4 for cholesterol 3-sulfate.
Galectin-4 binds to glycosphingolipids carrying 3-O-sulfated Gal residues, and it co-localizes on the cell surface of human colonic adenocarcinoma cells with glycosphingolipids carrying SO(-)(3)-->3Galbeta1-->3(GalNAc) residues (Ideo, H., Seko, A., and Yamashita, K. (2005) J. Biol. Chem. 280, 4730-4737). In the present study, it was found that galectin-4 also binds to cholesterol 3-sulfate, which has no beta-galactoside moiety. This characteristic of galectin-4 is unique within the galectin family. The site-directed mutated galectin-4-R45A had diminished binding ability toward cholesterol 3-sulfate, suggesting that Arg(45) of galectin-4 is indispensable for cholesterol 3-sulfate recognition. Gel filtration and chemical cross-linking experiments revealed that some galectin-4 exists as dimers, and this multivalency seemed to enhance its avidity for cholesterol 3-sulfate binding. Cholesterol 3-sulfate and sulfatide co-existed with galectin-4 in detergent-insoluble fractions of porcine esophagus and intestine, respectively. These results suggested that not only sulfated glycosphingolipids but also cholesterol 3-sulfate are endogenous ligands for galectin-4 in vivo.
Ideo
Hiroko
H
Innovative Research Initiatives, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.
Seko
Akira
A
Yamashita
Katsuko
K
D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D045744:Cell Line, Tumor; D002788:Cholesterol Esters / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000378:metabolism; D019281:Dimerization; D004947:Esophagus / Q000378:metabolism; D037541:Galectin 4 / Q000737:chemistry*; D037161:Galectins / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D002788:Cholesterol Esters; D037541:Galectin 4; D037161:Galectins; D001120:Arginine; C007045:cholesteryl sulfate