Galectin-1: Oligomeric structure and interactions with polylactosamine

Galectin-1 is a member of the galectin-1 family of lectins that is able to form a homodimer of 14 kDa subunits and each subunit has a single carbohydrate-binding site. The lectin is unusual in that it is synthesized in the cytosol of mammalian cells where it accumulates in a monomeric form. The lectin is actively, but slowly secreted (t(1/2)approximate to 20 h), and the secreted form requires glycoconjugate ligands to properly fold and acquire stability. The functional lectin exists in a monomer-dimer equilibrium with a K-d of similar to 7 mu M and the equilibration rate is rather slow (t(1/2)approximate to 10 h). To explore the mechanism of dimerization and functional differences between monomeric and dimeric forms of the galectin-1, specific mutations were made in the extreme N-terminus involved in subunit interactions. Two of these mutants, termed N-Gal-1 and V5D-Gal-1, are functional monomers at low concentrations (<60 mu M), but they dimerize at high concentrations. The dimeric forms of native and mutated galectin-1 can be covalently cross-linked to generate non-dissociable forms of galectin-1 that are extremely potent agglutinins. In contrast, the monomeric forms lack agglutinating activity, but they can compete with the dimeric forms of the lectin and block binding of the dimers. Galectin-1 binds to lactose Gal beta 1-->4Glc and N-acetyllactosamine Gal beta 1-->4GlcNAc with relatively low affinity (K-d in the range of 90-100 mu M), but the lectin binds to glycoproteins containing polylactosamine sequences [-->3Gal beta 1-->4GlcNAc beta 1-->](n) with high affinity (K-d approximate to 1 mu M). The lectin does not require terminal non-reducing galactose residues in polylactosamines for recognition. Polylactosamine sequences are selectively expressed on glycoproteins, such as laminin and lysosome-associated membrane proteins (LAMPs). The glycoproteins selectively recognized by galectin-1 may serve as potential ligands through which the lectin promotes cellular adhesion and cell signaling.