Two galactose-binding receptors, the hepatic asialoglycoprotein receptor
(ASGPR) and the macrophage galactose lectin (MGL) have been investigated. The
ASGPR is believed to function in glycoprotein clearance from serum while MGL is
involved in recognition of pathogens and tumours and in signalling and
immunomodulation. This work describes the analysis of the specificity, structure and
organisation of both receptors in humans and the two MGLs in mice.
The ligand-binding properties of the two subunits of the ASGPR as well as
MGL have been separately tested in glycan array analysis. The results show that
primary binding to ligands in the human ASGPR occurs via the ASGPR-1 subunit.
MGLs have different specificities even though they are highly similar in sequence and
the two mouse MGLs differ markedly from the single MGL in humans and in rats. One
of the mouse MGLs has a similar specificity to ASGPR-1 that evolved independently.
Hydrodynamic studies of ASGPR-1 revealed that it can form homo-oligomers
and circular dichroism analysis of the neck fragment showed that it has a coiled-coil
structure. Hetero-oligomer formation was monitored using a mutant version of ASGPR1
that allows purification of the complex using double-affinity chromatography on
galactose and mannose. Hetero-oligomers containing both types of subunits are more
stable than homo-oligomers. The results suggest a model that can account for the
variable subunit stoichiometries observed by various investigators. Hydrodynamic
studies and circular dichroism of MGL suggest that the extracellular domain of the
human protein is an oligomer not as stable as previously thought, and that its neck is a
coiled-coil structure. For both receptors, transmembrane and cytoplasmic domains as
well as glycosylation may have a role in their stability.
The ability of MGL to recognise pathogen glycans was demonstrated using
Trichinella spiralis secretions. It was found that similar glycoproteins are bound by the
human and mouse receptors.