5FJV

Crystal structure of the extracellular domain of alpha2 nicotinic acetylcholine receptor in pentameric assembly

Summary for 5FJV

• Entry DOI: 10.2210/pdb5fjv/pdb
• Descriptor: NEURONAL ACETYLCHOLINE RECEPTOR SUBUNIT ALPHA-2, EPIBATIDINE (2 entities in total)
• Functional Keywords: acetylcholine-binding protein, nachr, extracellular domain, nicotinic acetylcholine receptor, epibatidine, agonist, alpha2
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein: Q15822
• Total number of polymer chains: 5
• Total formula weight: 126495.43

Authors

Giastas, P.,Kouvatsos, N.,Chroni-Tzartou, D.,Tzartos, S.J. (deposition date: 2015-10-13, release date: 2016-08-10, Last modification date: 2024-10-23)

Primary citation

Kouvatsos, N.,Giastas, P.,Chroni-Tzartou, D.,Poulopoulou, C.,Tzartos, S.J.
Crystal Structure of a Human Neuronal Nachr Extracellular Domain in Pentameric Assembly: Ligand-Bound Alpah2 Homopentamer.
Proc.Natl.Acad.Sci.USA, 113:9635-, 2016

PubMed Abstract: In this study we report the X-ray crystal structure of the extracellular domain (ECD) of the human neuronal α2 nicotinic acetylcholine receptor (nAChR) subunit in complex with the agonist epibatidine at 3.2 Å. Interestingly, α2 was crystallized as a pentamer, revealing the intersubunit interactions in a wild type neuronal nAChR ECD and the full ligand binding pocket conferred by two adjacent α subunits. The pentameric assembly presents the conserved structural scaffold observed in homologous proteins, as well as distinctive features, providing unique structural information of the binding site between principal and complementary faces. Structure-guided mutagenesis and electrophysiological data confirmed the presence of the α2(+)/α2(-) binding site on the heteromeric low sensitivity α2β2 nAChR and validated the functional importance of specific residues in α2 and β2 nAChR subunits. Given the pathological importance of the α2 nAChR subunit and the high sequence identity with α4 (78%) and other neuronal nAChR subunits, our findings offer valuable information for modeling several nAChRs and ultimately for structure-based design of subtype specific drugs against the nAChR associated diseases.

PubMed: 27493220
DOI: 10.1073/PNAS.1602619113

Experimental method

X-RAY DIFFRACTION (3.2 Å)