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Publication Abstract from PubMed

The beta3 subunit of nicotinic acetylcholine receptors (nAChRs) participates in heteropentameric assemblies with some alpha and other beta neuronal subunits forming a plethora of various subtypes, differing in their electrophysiological and pharmacological properties. While beta3 has for several years been considered an accessory subunit without direct participation in the formation of functional binding sites, recent electrophysiology data have disputed this notion and indicated the presence of a functional (+) side on the extracellular domain (ECD) of beta3. In this study, we present the 2.4 A resolution crystal structure of the monomeric beta3 ECD, which revealed rather distinctive loop C features as compared to those of alpha nAChR subunits, leading to intramolecular stereochemical hindrance of the binding site cavity. Vigorous molecular dynamics simulations in the context of full length pentameric beta3-containing nAChRs, while not excluding the possibility of a beta3 (+) binding site, demonstrate that this site cannot efficiently accommodate the agonist nicotine. From the structural perspective, our results endorse the accessory rather than functional role of the beta3 nAChR subunit, in accordance with earlier functional studies on beta3-containing nAChRs.

Structural Insights into the Role of beta3 nAChR Subunit in the Activation of Nicotinic Receptors.,Giastas P, Papakyriakou A, Tsafaras G, Tzartos SJ, Zouridakis M Molecules. 2022 Jul 20;27(14). pii: molecules27144642. doi:, 10.3390/molecules27144642. PMID:35889515^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.