Cell membrane receptor-ligand

The general types of protein-protein interactions that occur in cells include receptor-ligand, enzyme-substrate, multimeric complex formations, structural scaffolds, and chaperones. However, proteins interact with more targets than just other proteins. Protein interactions can include protein-protein or protein-peptide, protein-DNA/RNA or protein-nucleic acid, protein-glycan or protein-carbohydrate, protein-lipid or protein-membrane, and protein-small molecule or protein-ligand. It is likely that every molecule within a cell has some kind of specific interaction with a protein. 

Calcineurin is part of a signaling pathway that is activated by a rise in intracellular calcium upon ligand binding to a cell membrane receptor. The rise in Ca activates calcineurin s phosphatase activity, which dephosphorylates cytoplasmic NF-AT transcription factor family members. Dephosphorylated NF-AT-members enter the nucleus and bind to DNA in cooperation with other transcription factors, e.g. AP-1. By this way many target genes in diverse tissues can be activated. 

The extracellular domain of cell membrane receptors can be produced recombi-nantly and used as a therapeutic product. The soluble receptor can be used to bind and neutralize the receptor s endogenous ligands (e.g., etanercept), or it can be used for stimulation of a co-receptor (e.g., abatacept). Soluble receptors are typically produced as IgG Fc fusion proteins to extend the half-life of the receptor in circulation. 

Numerous applications have been reported in the literature on the use of cell membrane receptors which require the use of ligand bilayer or phospholipid vesicles to maintain functionality, but other immobilization methods were also successfully used. The biosensing of e.g. acetylcholine and cholinergies has been reported with different transducers (ISFETs, interdigitated electrodes with measurements of capacity changes and optical fiber optode with fluorescence detection). 

EXAMPLE 6.5 Inositol trisphosphate (IP3) is often produced by cells in response to the binding of an extracellular ligand to a cell membrane receptor (see Sec. 6.3). Receptors for IP3 are located on the membranes of the endoplasmic reticulum. Binding of IP3 to these receptors leads to the release of Ca + from stores in the lumen of the endoplasmic reticulum. The IP3 receptor is therefore an example of a ligand-gated ion channel (see below)... 

Figure 5. General two-step fluidity hypothesis for the mechanism of modulation of effectors in cell membranes by ligands. The central feature is that the receptors and the effectors are discrete and separate structures that acquire specificity and affinity for complex formation only after the receptor has been occupied by the ligand. These structures can combine after binding of the ligand because of the fluidity of cell membranes. The ligand binding sites of the receptor are on the external face, exposed to the aqueous medium, and the active site of the effector (enzyme) is facing inward toward the cytoplasm of the cell. After Cuatrecasas (124).

Figure 4.30. Schematic illustration of a cell receptor ligand-"intelligent polymer conjugate binding to the cell membrane receptor, and stimulating various cell responses, including reversible cell culture on a surface, when stimulated to precipitate or redissolve [ 128 ].

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