An Unusual Carbohydrate Binding Site Revealed by the Structures of Two Maackia amurensis Lectins Complexed with Sialic Acid-containing Oligosaccharides

Abstract

Seeds from the legume tree Maackia amurensis contain two lectins that can agglutinate different blood cell types. Their specificity toward sialylated oligosaccharides is unique among legume lectins; the leukoagglutinin preferentially binds to sialyllactosamine (␣NeuAc-(2-3)␤Gal(1-4)␤GlcNAc), whereas the hemagglutinin displays higher affinity for a disialylated tetrasaccharide (␣NeuAc(2-3)␤Gal(1-3)[␣NeuAc(2-6)]␣GalNAc). The three-dimensional structure of the complex between M. amurensis leukoagglutinin and sialyllactose has been determined at 2.75-Å resolution using x-ray crystallography. The carbohydrate binding site consists of a deep cleft that accommodates the three carbohydrate residues of the sialyllactose. The central galactose sits in the primary binding site in an orientation that has not been observed previously in other legume lectins. The carboxyl group of sialic acid establishes a salt bridge with a lysine side chain. The glucose residue is very efficiently docked between two tyrosine aromatic rings. The complex between M. amurensis hemagglutinin and a disialylated tetrasaccharide could be modeled from the leukoagglutinin/sialyllactose crystal structure. The substitution of one tyrosine by an alanine residue is responsible for the difference in fine specificity between the two isolectins. Comparison with other legume lectins indicates that oligosaccharide specificity within this family is achieved by the recycling of structural loops in different combinations.

After shrinkage apoptotic cells expose internal membrane-derived epitopes on their plasma membranes

“…MAL I specifically binds to carbohydrate chains containing sialic acid and particularly to the aNeu5Ac(2-3)bGal (1-4)GlcNAc/Glc sequence. 22 MAL I has a high affinity for structures of mature glycoproteins. The terminal residues of oligosaccharides of mature glycoproteins are typically formed by sialic acid residues.…”

Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential

“…the highly metastatic breast cancer cell line MDA-MB-231 had higher expression of α2,3-sialic acid residues compared to t-47D and McF-7 depending on the mrnA levels of α2,3-st genes. the MAl (lectin from Maackia amurensis) specifically binding the sialylα2,3galβ1,4glcnAc/glc trisaccharide sequence (27). Furthermore, it can bind to certain sialylation residues that carry out various functions such as cell adhesion, invasion and migration.…”

Diversity in cell surface sialic acid presentations: implications for biology and disease

“…Preparations called 'MAA' are typically unspecified mixtures of two Maackia lectins, that is, one originally identified as a 'leukoagglutinin' (MAL) and a second one, a 'hemagglutinin' (MAH). [47][48][49] As these two lectins have differing specificity, the significance of any published results using 'MAA' preparations must be interpreted cautiously. A further complication arises because the MAL lectin is sometimes sold as 'MAL-I' and MAH as 'MAL-II'.…”