Agonist-binding domain

While the agonist binding domain is thought to be within the transmembrane domains for the monoamine and nucleotide receptors, neuropeptides are thought to bind close to the membrane surface on the extracellular domains of the receptor. It is still not clear whether non-peptide antagonists bind at the same or a different site on the receptor. 

Brauner-Osbome, H., Jensen, A. A., Sheppard, P. O., O Hara, P., and Krogsgaard-Larsen, P. (1999) The agonist-binding domain of the calcium-sensing receptor is located at the amino-terminal domain. J. Biol. Chem. 274,18382-18386. 

Madden, D. R., Abele, R., Andersson, A., and Keinanen, K. (2000). Large-scale expression and thermodynamic characterization of a glutamate receptor agonist-binding domain. Eur. J. Biochem. 267, 4281-4289. 

Nanao, M.H., Green, T, Stem-Bach, Y., Heinemann, S.E, and Choe, S. 2005. Stmcture of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid. PNAS 102, 1708-1713. 

Desensitisation is controlled in part by alternative splicing of the so-called flip and flop region in the loop between TM3 and TM4 [76]. The presence of glycosylation sites [77-79] and at least part of the agonist binding domain [80] in the same loop suggests its extracellular location. 

In the resting (closed) state, the ion channel is occluded by a hydrophobic girdle that constitutes a barrier to ion permeation. Agonist binding in the extracellular domain promotes a conformational change that results in a rotational movement of the M2 helices lining the pore, widening the pore by A. This results... 

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. 

In the monoamine receptors the ligand-binding domain is located within the transmembrane helices. A pocket is formed between TM3, TM5 and TM6 where the agonist binds. A conserved aspartate residue in TM3 (Asp-113 in the /(-adrenoceptor) and a... 

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