8ci2

human alpha7 nicotinic receptor in complex with the C4 nanobody under sub-saturating conditions

spinqualitylabelsall models 8ci2, resolution 4.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ci2 is a 8 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.4Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ACHA7_HUMAN 15q13.3 microdeletion syndrome. Function ACHA7_HUMAN After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin. Publication Abstract from PubMed The human alpha7 nicotinic receptor is a pentameric channel mediating cellular and neuronal communication. It has attracted considerable interest in designing ligands for the treatment of neurological and psychiatric disorders. To develop a novel class of alpha7 ligands, we recently generated two nanobodies named E3 and C4, acting as positive allosteric modulator and silent allosteric ligand, respectively. Here, we solved the cryo-electron microscopy structures of the nanobody-receptor complexes. E3 and C4 bind to a common epitope involving two subunits at the apex of the receptor. They form by themselves a symmetric pentameric assembly that extends the extracellular domain. Unlike C4, the binding of E3 drives an agonist-bound conformation of the extracellular domain in the absence of an orthosteric agonist, and mutational analysis shows a key contribution of an N-linked sugar moiety in mediating E3 potentiation. The nanobody E3, by remotely controlling the global allosteric conformation of the receptor, implements an original mechanism of regulation that opens new avenues for drug design. An original potentiating mechanism revealed by the cryo-EM structures of the human alpha7 nicotinic receptor in complex with nanobodies.,Prevost MS, Barilone N, Dejean de la Batie G, Pons S, Ayme G, England P, Gielen M, Bontems F, Pehau-Arnaudet G, Maskos U, Lafaye P, Corringer PJ Nat Commun. 2023 Sep 25;14(1):5964. doi: 10.1038/s41467-023-41734-4. PMID:37749098 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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