Galectin-8: On the road from structure to functions

Abstract

We have recently cloned and expressed a novel mammalian lectin of the galectin family and named it galectin-8 [Hadari et al. (1995) J. Biol. Chem. 270, 3447-3453], Galectin-8 is a 35 kDa protein, made of two domains of ∼140 amino-acids, each containing a single carbohydrate recognition domain (CRD). These domains are joined by a ∼30 amino acids 'link peptide'. Galectin-8 is a widely expressed protein present in liver, heart, muscle, kidney and brain. Native galectin-8 exists as a monomer, that is tightly associated to yet undefined cellular constituent. A conserved Arg residue which forms part of the sugar-binding site of all galectins, including the C-terminal CRD of galectin-8, is replaced with Ile90 at the N-terminal CRD of galectin-8. This substitution markedly changes the predicted surface of the N-terminal CRD, creating an extended hydrophobic pocket that can accommodate hydrophobic glycoconjugates. As such, the two CRDs of galectin-8 are expected to be structurally different and to interact with two different types of carbohydrates. Hence, galectin-8 is a naturally-occurring, ubiquitous, bifunctional mammalian lectin that might complex glycoconjugates of different types.