9qtn

Human alpha7 nicotinic receptor in complex with the F1 nanobody

spinqualitylabelsall models 9qtn, resolution 2.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9qtn is a 10 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 2.28Å Ligands: BMA, FUC, MAN, 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 alpha7 nicotinic receptors are neurotransmitter-gated ion channels involved in neurological and inflammatory diseases. Ligands acting on its neurotransmitter binding site and on the channel domain of alpha7 have been extensively developed, yielding a wide range of orthosteric effectors and allosteric positive modulators. Here, we present the functional and structural characterization of two camelid antibody fragments, or nanobodies, F1 and E6, that inhibit alpha7 activity by acting as negative allosteric modulators, an underrepresented class of ligands. Cryo-EM structures of the nanobodies in complex with alpha7 show that both nanobodies form a pentameric bundle at the apex of the receptor, each nanobody interacting through a conserved set of residues at alpha7 subunit interfaces. Electrophysiological experiments suggest that E6 inhibits the activity of alpha7 by stabilizing its resting conformation, and that internanobodies interactions are key to its activity. Those two nanobodies expand the toolbox for human alpha7 modulation, opening new possibilities for its pharmacological control with far reaching potentialities in clinics. Discovery and mechanism of negative allosteric modulation of the alpha7 nicotinic acetylcholine receptor by nanobodies.,Barilone N, Vangelatou M, Marouf FZ, Dejean de la Batie G, Li Q, Lafaye P, Ayme G, Corringer PJ, Prevost MS Proc Natl Acad Sci U S A. 2026 Jan 27;123(4):e2514734123. doi: , 10.1073/pnas.2514734123. Epub 2026 Jan 23. PMID:41576092 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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