C-Type Lectins Family

Abstract

Historically the C-Type lectins (CLEC) or C-type lectin receptors (CLR) form a family of Ca2+ dependent carbohydrate binding proteins which have a common sequence motif of 115–130 amino acid residues, referred to as the carbohydrate recognition domain (CRD). The C-type designation is from their requirement for calcium for binding. The C-type lectin superfamily is a large group of proteins which is characterized as having at least one carbohydrate recognition domain (CRD), which has been found in more than 1,000 proteins, and it represents a ligand-binding motif that is not necessarily restricted to binding sugars (Drickamer 1999). Proteins that contain C-type lectin domains have a diverse range of functions including cell-cell adhesion, immune response to pathogens and apoptosis. However, many C-type lectins actually lack calcium- and carbohydrate-binding elements and thereby have been termed C-type lectin-like proteins. The CRD has four cysteines that are perfectly conserved and involved in two disulfide bonds. The CRD has been found in various kinds of proteins such as hepatic asialoglycoprotein receptor, lymphocyte IgE receptor, mannose binding protein, selectins (Drickamer 1999; Lasky et al. 1989) and proteoglycan core protein. Their functions include complement activation, endocytosis, cell recognition, defense mechanism, and morphogenesis (Drickamer 1999; Weis et al. 1998). Many evolutionarily related sequences belonging to the C-type lectins do not show overall sequence similarity. However, they have been classified on the basis of four cysteine residues, being involved in disulfide bridging, which are the trademark of this domain type. The framework surrounding this domain type can be very different from its C-terminal location in the collectins. The monomeric and membrane bound selectins have an N-terminal C-type lectin domain that mediates adhesion between certain cell types through carbohydrate binding. Other proteins, such as phospholipase A2 receptor and the macrophage mannose receptor, contain multiple copies of C-type lectin domains within a single polypeptide. Proteins possessing C-type lectin-like domain (CTLD) type are not necessarily lectins. Type II antifreeze protein present in some arctic fish and the mammalian pancreatic stone protein bind to and inhibit the growth of ice and calcium carbonate crystals, respectively (Hakansson and Reid 2000) and hence are not exactly CLEC but form a part of CTLD.