Group II - Type 2 Receptors

Introduction
Sequence alignments: Human Human/Mouse

Group II domain organizationThe type 2 receptor group of CTLD-containing cell surface proteins has over a dozen members in humans and slightly more in the mouse.  Many of the proteins are expressed on haematopoietic cell types, particularly macrophages and dendritic cells, but others are found on endothelia or hepatocytes.  Type 2 receptor polypeptides have a single C-terminal CTLD, which is separated from the transmembrane domain by a neck region.  In some cases the neck is short, but it is often extended with heptad repeats that mediate trimer- or tetramerization of the polypeptide through the formation of a coiled-coil of alpha-helices.  In the scavenger receptor C-type lectin (SRCL), the neck is further extended to include a collagen-like domain.  The cytoplasmic tails of type 2 receptors in many cases contain sequence motifs which direct endocytosis or which interact with intracellular signalling proteins. 

Recognition of either endogenous or pathogen-related carbohydrates is central to the function of many type 2 receptors.  Members of this group have roles in cell-cell interactions in the immune system (dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN)), clearance of serum glycoproteins (asialoglycoprotein receptor), regulation of immunoglobulin E production (CD23), and antigen uptake (DC-SIGN, langerin and others).  Several type 2 receptors remain poorly understood, but may be involved in pathogen recognition or antigen uptake.  Some type 2 receptors may promote infection by certain pathogens: for example, DC-SIGN enhances infection by viruses including human immunodeficiency virus (HIV)-1.

The CTLDs in most type 2 receptors bind carbohydrates, although sugar-binding activity remains to be investigated in some less well-characterized members of the group.  CD23 is the only well-documented type 2 receptor that does not appear to bind carbohydrates; in this case, the CTLD binds immunoglobulin E through protein-protein interactions.  CRDs of both the mannose- and galactose-binding subtypes are found within the type 2 receptor group.  Some have simple binding sites accommodating only terminal sugar residues, whereas others have extended sites with specificity for more complex structures, such as the Lewis antigens.

 

Structure of human DC-SIGN with bound oligosaccharide (GlcNAc-Man3-GlcNAc)

Ca2+ ions are shown in dark blue.  The oligosaccharide is coloured by atom: black, carbon; red, oxygen; blue, nitrogen.  Protein Data Bank structure ID: 1K9I.

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This page last updated:
Wednesday, 01 January 2014
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Contact information: This site is supported by:
 
Kurt Drickamer
Division of Molecular Biosciences
Faculty of Natural Sciences
Imperial College London
 
Email: k.drickamer@imperial.ac.uk