Mannose Receptor Family: R-Type Lectins

Abstract

R-type lectins exist ubiquitously in nature and mainly bind to galactose unit of sugar chains. Originally found in plant lectin, Ricin, the R-type lectin domain is found in several animal lectins, including the members of mannose receptor (MR) family, and in some invertebrate lectins (discussed in Chap. 14). The R-type domain contained in these proteins is the CRD, which is also termed a carbohydrate-binding module (CBM) and has been placed in the CBM13 family in the CAZy database (carbohydrate-active enzymes database). While the A chain in ricin has eight α-helices and eight β-strands, and is the catalytic subunit, the B chain contains R-type lectin domains, has two tandem CRDs that are about 35 A apart and have a shape resembling a barbell, with one binding domain at each end. Each R-type domain has a three-lobed organization that is a β-trefoil structure (from the Latin trifolium meaning “three-leaved plant”). The β-trefoil structure probably arose evolutionarily through gene fusion events linking a 42-amino-acid peptide subdomain that has galactose-binding activity. The three lobes are termed α, β, and γ and are arranged around a threefold axis. Conceivably, each lobe could be an independent binding site, but in most R-type lectins only one or two of these lobes retain the conserved amino acids required for sugar binding. The R-type domain is also found in pierisin-1, which is a cytotoxic protein from the cabbage butterfly Pieris rapae, and in the homologous protein pierisin-2, from Pieris brassicae. Tandem R-type motifs are found in some other R-type family members. For example, Limulus horseshoe crab coagulation factor G has a central R-type lectin domain, which is flanked at the amino terminus by a xylanase Z-like domain and at the carboxyl terminus by a glucanase-like domain. In this chapter we will restrict our discussion to R-type lectins of mannose receptor family, which comprises also of endocytic receptors.