C-type lectins (C-type Lectins) are a class of proteins that can bind to sugars. They differ from other types of lectins in that they contain a calcium-dependent sugar recognition region of approximately 120 amino acid sequences. C-type lectin is a class of protein superfamily containing calcium ion (Ca2+)-dependent carbohydrate recognition domain (CRD).
Figure 1. Protein structure of C-type lectins.
C-type lectins (C-type Lectins) are a class of proteins that can bind to sugars. They differ from other types of lectins in that they contain a calcium-dependent carbohydrate recognition domain (CRD) of approximately 120 amino acid sequences. Type C lectin is a class of protein superfamily containing calcium ion (Ca2+)-dependent carbohydrate recognition domain (CRD) and is an important pattern-recognition receptor (PRR) in the innate immune system. Most C-type lectins are mainly distributed in hepatopancreas and blood cells; C-type lectins that are highly expressed in hepatopancreas tend to be tissue-specific, while C-type lectins that are highly expressed in other tissues are more likely to be widely distributed.
According to the subcellular localization of type C lectin, it can be divided into two types: soluble and membrane type C lectin. In mammals, C-type lectins located on the cell surface are often referred to as C-type lectinreceptors (CLR). In the same way, classic C-type lectins are called classic C-type lectin receptors; non-classical C-type lectins are called non-classical C-type lectin receptors (non -classic C-type lectin receptor), also known as C-type lectin-like receptor.
Soluble C-type lectins including electican, collectins, tetranectins, REGs, EMBP, SEEC, and CBCP/Frem1 /QBRICK family. Among the soluble C-type lectins, the biological function of the collectins (collagen lectin) family is most clearly studied. The N-terminus of collectins contains a collagen-like region and can be assembled into oligomers containing multiple subunits. Nine collectins family members were identified, including mannose-binding Lectin (MBL), conglutinin, lung surfactant proteins SP-A and SP-D, and CL-43, CL-46, CL-P1, CL-L1, and CL-K1. CL-L1 and CL-P1 are expressed on the surface of the cell membrane, and the rest are soluble proteins.
Most C-type lectins are located on the surface of cell membranes and can be classified into classic and non-classical C-type lectins. As a cell surface receptor, it can recognize a wide range of ligands, including sugar chains, proteins and lipids. These proteins act as adhesion receptors, signal receptors, or phagocytic receptors, participate in cell adhesion, recognition, phagocytosis and elimination of foreign / endogenous substances, and intracellular signal transduction. They maintain physiological functions such as the homeostasis of the body, and It plays an important role in diseases such as infection, inflammation, and tumor immunity.
The CTLD of classical C-type lectins contains a Ca2+ binding motif. Ca2+ is involved in CTLD recognition of carbohydrates and plays an important role in maintaining the correct folding of CTLD. Classical C-type lectins on the surface of cell membranes contain many members that differ in specificity and biological function of their recognition ligands.
Compared with the classical C-type lectin receptor, the non-classical C-type lectin receptor has a similar CTLD structure, but this domain lacks a conserved motif that binds to Ca2+, and the recognition ligand is Ca2+ independent. Genes encoding nonclassical C-type lectin-like receptors are mainly located in the NK gene complex (NKC). Humans are located on chromosome 12 and mice are located on chromosome 6. Nonclassical C-type lectin-like receptors have evolved to recognize non-carbohydrate ligands, including proteins and lipids, such as major class I histocompatibility antigens or related factors, and oxidized low-density lipoprotein. But there are some that can recognize carbohydrates through mechanisms different from classic C-type lectin receptors.
Examples of NKG2D
NKG2D is a transmembrane protein belonging to the CD94/NKG2 family of C-type lectin-like receptors. NKG2D is encoded by the KLRK1 gene, which is located in the NK gene complex (NKC) on mouse and human chromosome 12. The human NKG2D receptor complex is assembled into a hexameric structure. NKG2D itself forms a homodimer, and its extracellular domain is used for ligand binding. Each NKG2D monomer is associated with a DAP10 dimer. This connection can be maintained through the interaction of positively charged arginine present in the NKG2D transmembrane fragment with negatively charged aspartic acid ions in the two transmembrane regions of the DAP10 dimer.
Figure 2. Protein structure of NKG2D.
Type C lectin domain family 1 component B is a protein that, in humans, is encoded by the CLEC1B gene. Natural killer (NK) cells express multiple calcium-dependent (type C) lectin-like receptors, such as CD94, which interact with major class I molecules with complex histocompatibility or inhibit or activate cytotoxicity and cytokines secretion. CLEC2 is a type C lectin-like receptor expressed in myeloid cells and NK cells.
Figure 3. Protein structure of CLEC1B.
CD23, also known as Fc Small RII, or FcεRII, is a "low-affinity" receptor pair of IgE, an antibody involved in allergy and antiparasites, and is important in the regulation of IgE levels. Unlike many antibody receptors, CD23 is a type C lectin. It is found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells and platelets. CD23 comes in two forms: CD23a and CD23b. CD23a is present on follicular B cells, while CD23b requires IL-4 to be expressed on T cells, monocytes, Langerhans cells, eosinophils, and macrophages.
Figure 4. Protein structure of CD23.
The C-type lectin domain family 4M is a protein that is encoded in humans by the CLEC4M gene. CLEC4M is also designated as CD299 (differentiated cluster 299). This gene encodes L-SIGN (liver/lymph node-specific intracellular adhesion molecule 3 captures non-integrin), a type II integral membrane protein, and has 77% identity to the HIV gp120 binding protein CD209 antigen. Like CD209, this protein effectively binds intercellular adhesion molecule 3 (ICAM3) and HIV-1 gp120, which enhances HIV-1 infection of T cells. The gene clusters with the CD209 and CD23/FCER2 genes and is located at 19p13.3. Multiple alternative splicing transcriptional variants of this gene have been discovered, but the biological effectiveness of certain variants has not been determined.
Figure 5. Protein structure of CLEC4M.
Walker JR.; et al. X-ray crystal structure of a galactose-specific C-type lectin possessing a novel decameric quaternary structure. Biochemistry.2004, 43 (13): 3783–92.