Abstract
The fruiting body of the edible mushroom Agrocybe cylindracea contains a proto-type galectin named ACG, which shows affinity to a wide range of β-galactosides. Unlike other galectins, it also binds to disaccharides (GalNAcα1-3Gal/GalNAc) found in blood group A and Forssman epitopes. Structurally, ACG lacks an evolutionarily conserved Asn located on the S4 strand (Ala64) but is compensated for by Asn46, which is located on the extended loop region unique to this galectin. A recent site-directed mutagenesis study revealed that the N46A mutant had selective affinity to oligosaccharides containing GalNAcα1-3Gal/GalNAc epitopes (Hu et al., (2013) Biochem. J., 453, 261–270). Taking into consideration the previous observation that Pro45 takes the cis conformation, Hu et al. assumed that ACG has evolved to attain two conformations at the imide group of Pro45: a cis conformation, where it can recognize β-galactosides, and a Pro45-tras conformation while it binds to the unique GalNAcα1-3Gal/GalNAc. The proposed dual recognition mechanism was proved through further site-directed mutagenesis and X-ray crystallography analysis. Notably, N46A recognizes even non-reducing terminal disaccharides, GalNAcα1-3Gal/GalNAc. Thus, the one face of this “Janus-type” lectin fulfills the conventional definition of galectins, whereas the other face does not. A possible scenario of galectin deviation is discussed.
