PROSITE documentation PDOC50231

Lectin domain of ricin B chain profile

Primary structure analysis has shown the presence of a similar domain in many carbohydrate-recognition proteins like plant and bacterial AB-toxins, glycosidases or proteases [1,2,3]. This domain, known as the ricin B lectin domain, can be present in one or more copies and has been shown in some instance to bind simple sugars, such as galactose or lactose.

The ricin B lectin domain is composed of three homologous subdomains of 40 amino acids (α, β and γ) and a linker peptide of around 15 residues (lambda). It has been proposed that the ricin B lectin domain arose by gene triplication from a primitive 40 residue galactoside-binding peptide [4,5]. The most characteristic, though not completely conserved, sequence feature is the presence of a Q-W pattern. Consequently, the ricin B lectin domain as also been refered as the (QxW)3 domain and the three homologous regions as the QxW repeats [2,3]. A disulfide bond is also conserved in some of the QxW repeats [2].

The 3D structure of the ricin B chain has shown that the three QxW repeats pack around a pseudo threefold axis that is stabilised by the lambda linker [4]. The ricin B lectin domain has no major segments of a helix or β sheet but each of the QxW repeats contains an omega loop [5]. An idealized omega-loop is a compact, contiguous segment of polypeptide that traces a 'loop-shaped' path in three-dimensional space; the main chain resembles a Greek omega.

Some proteins containing a ricin B lectin domain are listed below [3]:

• Ricin, from Ricinus communis (Castor bean). Ricin belongs to a group of plant AB-toxins, which also contains agglutinin and abrin. Ricin is composed of a sugar-binding subunit (B chain) that attaches to galactose residues presented by cell surface glycoproteins or glycolipids and a subunit (chain A) with enzymatic activity that attacks and inactivates ribosomes. The B chain contains two ricin B lectin domains [4].
• Serine protease I (RPI) (EC 3.4.21.-), from Rarobacter faecitabidus [6]. RIP is a serine protease exhibiting lytic activity toward living yeast cells. It possess a ricin B lectin domain that is involved in mannose binding in its C terminal part.
• The bacterial AHH1/ASH4/HlyA/VVHA family of hemolysins. Bacterial hemolysins are exotoxins that attack blood cell membranes and cause cell rupture by mechanisms not clearly defined. Proteins belonging to this family possess one ricin B lectin domain.
• Glucan endo-1,3-β-glucanase (EC 3.2.1.39), from Oerskovia xanthineolytica. This yeast-lytic protein has a C-terminal ricin B lectin domain which appears to target the catalytic domain to yeast cell wall.
• Endo-1,4-β-xylanase A (EC 3.2.1.8) (gene xlnA), from Streptomyces. The C-terminal ricin B lectin domain has been proposed to bind to the polymeric substrate of this enzyme, but no carbohydrate binding data are available.
• The macrophage mannose receptor (MRC1), from mammals. MRC1 is a Type I membrane receptor protein that is expressed at the surface of mature macrophages. It binds mannose- and fucose-rich carbohydrate polymers and appears to mediate phagocytic uptake of foreign microorganisms. Its extracellular region contains 8 copies of the C-type lectin domain (see <PDOC00537>) and one ricin B lectin domain to which no sugar binding function has been ascribed so far [7].
• The AIM1 protein, from mammals. AIM1 is a member of the β- γ- crystallin superfamily and contains a C-terminal ricin B lectin domain. In human, it is associated with the control of tumorigenicity.
• Phospholipase A2 receptor, from mammals. This proteins contains 8 copies of the C-type lectin domain and one N-terminal ricin B lectin domain whose function is unknown.
• UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (EC 2.4.1.41) (gene GALNT1). This protein catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. This protein binds carbohydrate as a soluble substrate and contains one copy of the ricin B lectin domain.
• The 33-kDa hemagglutinin component of the botulinum neurotoxin complex. This protein has two copies of the ricin B lectin domain and agglutinates red blood cells.