Ligand protein receptors

Licitra, E. J., and Liu, J. O. (1996). A three-hybrid system for detecting small ligand—protein receptor interactions. Proc. Natl. Acad. Sci. USA 93, 12817—12821. 

In an extensive SFA study of protein receptor-ligand interactions, Leckband and co-workers [114] showed the importance of electrostatic, dispersion, steric, and hydrophobic forces in mediating the strong streptavidin-biotin interaction. Israelachvili and co-workers [66, 115] have measured the Hamaker constant for the dispersion interaction between phospholipid bilayers and find A = 7.5 1.5 X 10 erg in water. 

The ability of receptors to couple to G-proteins and initiate GTPase activity may also be independent of ligand. Thus, specific mutations in a- and P-adrenergic receptors have led to receptors that mediate agonist-independent activation of adenylyl cyclase (69,70). These mutations presumably mimic the conformational state of the ligand-activated receptor when they are activated conventionally by ligands. 

If there is a means to detect (i.e., radioactivity, fluorescence) and differentiate between protein-bound and free ligand in solution, then binding can directly quantify the interaction between ligands and receptors. 

The majority of functional assays involve primary signaling. In the case of GPCRs, this involves activation of G-proteins. However, receptors have other behaviors— some of which can be monitored to detect ligand activity. For example, upon stimulation many receptors are desensitized through phosphorylation and subsequently taken into the cell and either recycled back to the cell surface or digested. This process can be monitored by observing ligand-mediated receptor internalization. For... 

Cubic ternary complex model, a molecular model (J. Their. Biol 178, 151-167, 1996a 178, 169-182, 1996b 181, 381-397, 1996c) describing the coexistence of two receptor states that can interact with both G-proteins and ligands. The receptor/G-protein complexes may or may not produce a physiological response see Chapter 3.11. 

Meyer B, Peters T (2003) NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors. Angew Chem Int Ed Engl 42 864-890... 

Receptors permanently linked to an effector consist of proteins with an extracellular ligand-binding receptor domain and a signal-generating effector domain (Fig. 1). Most of these receptors are composed of two to five structurally related or identical subunits. Effectors can be enzymes or ion channels whose activities are stimulated by agonist binding without significant delay. 

Transmembrane Signaling. Figure 2 Membrane topology of receptors that are associated with effector proteins. Upon binding to their cognate ligands (cyan), receptor proteins without intramolecularly linked effector domain couple via transducer proteins (yellow) to or directly recruit and activate effector proteins (red). Notch receptors release their transducer domains upon proteolytic cleavage, a, p and y stand for G-protein a-, p- and y-subunits, respectively. 

There may be substantial variation both within and among species (e.g., in mice vs. humans) in the expression of various proteins, receptors and/or ligands that influence the activation of mast cells (or basophils or other potential effector cell types), or that can regulate the responsiveness of end organ target cells (e.g., bronchial or gastrointestinal smooth muscle cells, vascular endothelial cells) to potential mediators of anaphylaxis derived from mast cells. 

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