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Open data
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Basic information
| Entry | Database: PDB / ID: 9qtn | |||||||||||||||||||||
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| Title | Human alpha7 nicotinic receptor in complex with the F1 nanobody | |||||||||||||||||||||
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Keywords | MEMBRANE PROTEIN / Nicotinic receptor / Nanobody | |||||||||||||||||||||
| Function / homology | Function and homology informationsensory processing / synaptic transmission involved in micturition / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / acetylcholine-gated channel complex / regulation of amyloid fibril formation / chloride channel regulator activity / acetylcholine-gated monoatomic cation-selective channel activity ...sensory processing / synaptic transmission involved in micturition / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / acetylcholine-gated channel complex / regulation of amyloid fibril formation / chloride channel regulator activity / acetylcholine-gated monoatomic cation-selective channel activity / short-term memory / cation channel complex / acetylcholine binding / dendritic spine organization / regulation of amyloid precursor protein catabolic process / acetylcholine receptor signaling pathway / neurotransmitter receptor complex / positive regulation of amyloid-beta formation / positive regulation of protein metabolic process / negative regulation of amyloid-beta formation / response to amyloid-beta / ligand-gated ion channel signaling pathway / negative regulation of tumor necrosis factor production / modulation of excitatory postsynaptic potential / plasma membrane raft / monoatomic ion channel activity / toxic substance binding / monoatomic ion transport / negative regulation of cytokine production involved in inflammatory response / negative regulation of canonical NF-kappaB signal transduction / positive regulation of excitatory postsynaptic potential / positive regulation of long-term synaptic potentiation / response to nicotine / excitatory postsynaptic potential / regulation of membrane potential / synapse organization / cognition / memory / calcium channel activity / positive regulation of angiogenesis / intracellular calcium ion homeostasis / calcium ion transport / transmembrane signaling receptor activity / amyloid-beta binding / monoatomic ion transmembrane transport / chemical synaptic transmission / response to hypoxia / learning or memory / postsynaptic membrane / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAPK cascade / neuron projection / postsynapse / positive regulation of cell population proliferation / synapse / dendrite / endoplasmic reticulum membrane / signal transduction / protein homodimerization activity / membrane / plasma membrane Similarity search - Function | |||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() | |||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.28 Å | |||||||||||||||||||||
Authors | Barilone, N. / Vangelatou, M. / Marouf, F.Z. / Dejean de la Batie, G. / Ayme, G. / Lafaye, P. / Corringer, P.-J. / Prevost, M.S. | |||||||||||||||||||||
| Funding support | European Union, France, 2items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2026Title: Discovery and mechanism of negative allosteric modulation of the α7 nicotinic acetylcholine receptor by nanobodies. Authors: Nathalie Barilone / Maria Vangelatou / F Zahra Marouf / Gabrielle Dejean de la Bâtie / Qimeng Li / Pierre Lafaye / Gabriel Aymé / Pierre-Jean Corringer / Marie S Prevost / ![]() Abstract: α7 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 ...α7 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 α7 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 α7 activity by acting as negative allosteric modulators, an underrepresented class of ligands. Cryo-EM structures of the nanobodies in complex with α7 show that both nanobodies form a pentameric bundle at the apex of the receptor, each nanobody interacting through a conserved set of residues at α7 subunit interfaces. Electrophysiological experiments suggest that E6 inhibits the activity of α7 by stabilizing its resting conformation, and that internanobodies interactions are key to its activity. Those two nanobodies expand the toolbox for human α7 modulation, opening new possibilities for its pharmacological control with far reaching potentialities in clinics. | |||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9qtn.cif.gz | 463.3 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9qtn.ent.gz | 303.4 KB | Display | PDB format |
| PDBx/mmJSON format | 9qtn.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qt/9qtn ftp://data.pdbj.org/pub/pdb/validation_reports/qt/9qtn | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 53355MC ![]() 9qtoC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Protein / Antibody / Non-polymers , 3 types, 113 molecules ABCDEFGHIJ

| #1: Protein | Mass: 54154.391 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CHRNA7, NACHRA7 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P36544#2: Antibody | Mass: 14355.015 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #9: Water | ChemComp-HOH / | |
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-Sugars , 6 types, 15 molecules
| #3: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Polysaccharide | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source |
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-Details
| Has ligand of interest | N |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: Human nicotinic acetylcholine receptor alpha7 in complex with Nanobody F1 Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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| Molecular weight | Value: 0.325 MDa / Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.8 |
| Specimen | Conc.: 0.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Microscopy | Model: TFS TITAN THEMIS |
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| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
| Electron lens | Mode: OTHER / Nominal defocus max: 2750 nm / Nominal defocus min: 700 nm |
| Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
| EM software | Name: PHENIX / Version: 1.21_5207 / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.28 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 325670 / Symmetry type: POINT | ||||||||||||||||||||||||
| Atomic model building | Protocol: RIGID BODY FIT | ||||||||||||||||||||||||
| Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
| Displacement parameters | Biso mean: 90.48 Å2 | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi




Homo sapiens (human)

France, 2items
Citation



PDBj






FIELD EMISSION GUN