A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell.
Properties
The term co-receptor is prominent in literature regarding signal transduction, the process by which external stimuli regulate internal cellular functioning. The key to optimal cellular functioning is maintained by possessing specific machinery that can carry out tasks efficiently and effectively. Specifically, the process through which intermolecular reactions forward and amplify extracellular signals across the cell surface has developed to occur by two mechanisms. First, cell surface receptors can directly transduce signals by possessing both serine and threonine or simply serine in the cytoplasmic domain. They can also transmit signals through adaptor molecules through their cytoplasmic domain which bind to signalling motifs. Secondly, certain surface receptors lacking a cytoplasmic domain can transduce signals through ligand binding. Once the surface receptor binds the ligand it forms a complex with a corresponding surface receptor to regulate signalling. These categories of cell surface receptors are prominently referred to as co-receptors. Co-receptors are also referred to as accessory receptors, especially in the fields of biomedical research and immunology.
Co-receptors are proteins that maintain a three-dimensional structure. The large extracellular domains make up approximately 76–100% of the receptor. The motifs that make up the large extracellular domains participate in ligand binding and complex formation. The motifs can include glycosaminoglycans, EGF repeats, cysteine residues or ZP-1 domains. The variety of motifs leads to co-receptors being able to interact with two to nine different ligands, which themselves can also interact with a number of different co-receptors. Most co-receptors lack a cytoplasmic domain and tend to be GPI-anchored, though a few receptors have been identified which contain short cytoplasmic domains that lack intrinsic kinase activity.
Localization and function
Depending on the type of ligand a co-receptor binds, its location and function can vary. Various ligands include interleukins, neurotrophic factors, fibroblast growth factors, transforming growth factors, vascular endothelial growth factors and epidermal growth factors. Co-receptors prominent in embryonic tissue have an essential role in morphogen gradient formation or tissue differentiation. Co-receptors localized in endothelial cells function to enhance cell proliferation and cell migration. With such variety in regards to location, co-receptors can participate in many different cellular activities. Co-receptors have been identified as participants in cell signalling cascades, embryonic development, cell adhesion regulation, gradient formation, tissue proliferation and migration.
Some classical examples
CD family
The CD family of co-receptors are a well-studied group of extracellular receptors found in immunological cells. The CD receptor family typically act as co-receptors, illustrated by the classic example of CD4 acting as a co-receptor to the T cell receptor (TCR) to bind major histocompatibility complex II (MHC-II). This binding is particularly well-studied in T-cells where it serves to activate T-cells that are in their resting (or dormant) phase and to cause active cycling T-cells to undergo programmed cell death. Boehme et al. demonstrated this interesting dual outcome by blocking the binding of CD4 to MHC-II which prevented the programmed cell death reaction that active T-cells typically display. The CD4 receptor is composed of four concatamerized Ig-like domains and is anchored to the cell membrane by a single transmembrane domain. CD family receptors are typically monomers or dimers, though they are all primarily extracellular proteins. The CD4 receptor in particular interacts with murine MHC-II following the "ball-on-stick" model, where the Phe-43 ball fits into the conserved hydrophobic α2 and β2 domain residues. During binding with MHC-II, CD4 maintains independent structure and does not form any bonds with the TCR receptor.