By Qin Wang
This quantity of Current themes in Membranes makes a speciality of adrenergic receptor biology, starting with a assessment of prior successes and old views then extra discussing present common developments in adrenic receptor reports in numerous contexts. This ebook additionally contains discussions of the function and courting of adrenergic receptors to assorted structures and illnesses, constructing adrenergic receptor biology as a wanted, useful reference for researchers.
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Additional info for Advances in Adrenergic Receptor Biology, Volume 67 (Current Topics in Membranes)
Most other GPCRs have some level of constitutive activity and behave as discussed above, more like rheostats than switches. Different ligands can toggle 2. Organizational Complexity of b-adrenergic Receptor Signaling Systems 25 the receptor to different levels of activity and different ligands may drive other GPCRs into a distinct set of conformational states in contrast with the ‘‘one’’ ligand for rhodopsin. Thus the dynamics of receptor activation may be different depending on the particular ligand, G protein, or other signaling partner – that is, molecular context as we discuss below is critical for determining which states a given receptor can occupy.
Reconstitution of catecholamine-sensitive adenylate cyclase activity: Interactions of solubilized components with receptor-replete membranes. Proc Natl Acad Sci USA, 74, 3715–3719. , & Lefkowitz, R. J. (1993). A mutation-induced activated state of the beta2-adrenergic receptor. Extending the ternary complex model. J Biol Chem, 268, 4625–4636. , (1998). Neurabin-II/spinophilin. An actin filament-binding protein with one pdz domain localized at cadherin-based cell-cell adhesion sites. J Biol Chem, 273, 3470–3475.
The amino acids just below carazolol form a ‘‘toggle’’’ that stabilizes the inactive state of the receptor. Despite superposition of the toggle switch residues of b2AR with those of the inactive state of rhodopsin, TM-VI of the b2AR is slightly more tilted, most likely due to the opening of the ionic lock. Other b-adrenergic ligands found to be inverse agonists for AC but agonists for MAPK can be predicted to dock in the b2AR in a manner highly similar to that of carazolol (Audet & Bouvier, 2008).