Lectins are glycoproteins that can bind carbohydrates. These carbohydrate binding proteins serve a number of vital roles which are disucussed below.

Classification

There are a number of structurally distinct plant and animal lectin families. Lectins have been separated into various classes based on what type of carbohydrate they bind to. Schnorr (WO2004/090549). 

C-type lectins (selectins): There are 32 extracellular C-type lectins (selectins)

–Mannose-binding lectin (MBL) and ficolin: These proteins belong to the C-type lectin family (or collecitns) are are ocmposed of multiple subunits containing cysteine and collagen rich domains, an alpha helical coil and a highly conversed carboxy-temrinal carohydrate recognition domain (CRD). These lectins activate the lectin pathway of the complement system. 

I type (or sialic aicd) lectins: There are two I type (or sialic aicd) lectins that have been characterized. 

Biological Functions

(1) intracellular sorting: An example of this is lysosomal hydolases which are transported through the golgi and eventually end up in lysosomes. These hydrolases have a unique marker, Mannose-6-phosphate, which are recognized by M6P receptors in the trans-golgi.

(2) clearance of serum proteins; sialic acids on the nonreducing end of oligosccharide chains protects those proteins from rapid degradation in the serum. Exposure of galactose after removal of sialic acid render the protein susceptible to the binding of a receptor on hepatocytes which take up the complex by endocytosis and degrade it in lysosomes. Most peptide and proteins that are injected into humans are also rapidly degraded unless carbohydrate is attached. Proteins with manose or galactose as the nonreducing terminal sugar are rapidly recognized by mannose or galactose receptors. Pharmaceutical companies likeNeose are developing strategies to glycosylate proteins to improve serum half life, using chemical and enzymatic techniques.

(3) complement cascade; Mannose binding lectins found in the serum bind 3 adjacent mannose residues on the surface of invading pathogens which helps initiate the complement cascade. Host structures do not have 3 mannose residues this close together, and are not recognized. Mannose-binidng lectin (MBL) and ficolin, an MBL-like protein, activate the lecitn pathway of the complement system. These proteins belong to the C-type lectin family (or collectins) and are composed of multimple subunits containing cysteine and collagen-rich domains, an alpha helical coil and a highly conserved carboxy-terminal carbohydrate recognition domain (CRD). See the complement system for more detail. 

(4) cell-cell interaction and inflammation; The endothelium express which upon binding to their carboyhydrate containing receptors on neutrophils, initiate a rolling adhesion of neutrophils. The neutrophils in turn activate their integrins which bind to endotheilial ICAM permitting a firmer adhesion.

(5) dendritic cell function: It has been demonstrated that lectins function in dendritic cells to capture and direct antigens to specialized antigen-processing compartments within the cell, via receptor mediated endocytosis. Also, lectin-ligand interactions can modulate cytokine production by dendritic cells as well as the maturation state of those cells. One class of lectins that often appear are caclium dependent carbohydrate binding proteins, or “C-type lectins”. 

Applications

Companies like Glycominds have developed glycochips which allow detection of proteins or cells to particular oligosaccharide structures. These chips may prove useful for development of drugs that inhibit cell-cell interaction, such as occurs during inflammation.