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Yorodumi- PDB-8ci2: human alpha7 nicotinic receptor in complex with the C4 nanobody u... -
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-Basic information
Entry | Database: PDB / ID: 8ci2 | ||||||||||||||||||
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Title | human alpha7 nicotinic receptor in complex with the C4 nanobody under sub-saturating conditions | ||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / ion channel nanobody Nicotinic acetylcholine receptor | ||||||||||||||||||
Function / homology | Function and homology information sensory processing / dendrite arborization / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / response to acetylcholine / acetylcholine-gated channel complex / acetylcholine-gated monoatomic cation-selective channel activity / regulation of amyloid fibril formation / short-term memory / positive regulation of CoA-transferase activity ...sensory processing / dendrite arborization / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / response to acetylcholine / acetylcholine-gated channel complex / acetylcholine-gated monoatomic cation-selective channel activity / regulation of amyloid fibril formation / short-term memory / positive regulation of CoA-transferase activity / dendritic spine organization / acetylcholine binding / chloride channel regulator activity / regulation of amyloid precursor protein catabolic process / acetylcholine receptor signaling pathway / positive regulation of amyloid-beta formation / negative regulation of amyloid-beta formation / plasma membrane raft / modulation of excitatory postsynaptic potential / response to amyloid-beta / positive regulation of excitatory postsynaptic potential / negative regulation of tumor necrosis factor production / toxic substance binding / monoatomic ion transport / positive regulation of protein metabolic process / monoatomic ion channel activity / positive regulation of long-term synaptic potentiation / cognition / response to nicotine / synapse organization / calcium channel activity / memory / intracellular calcium ion homeostasis / positive regulation of angiogenesis / calcium ion transport / monoatomic ion transmembrane transport / amyloid-beta binding / postsynaptic membrane / postsynapse / positive regulation of MAPK cascade / positive regulation of ERK1 and ERK2 cascade / learning or memory / response to hypoxia / neuron projection / positive regulation of protein phosphorylation / positive regulation of cell population proliferation / synapse / signal transduction / protein homodimerization activity / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) Vicugna pacos (alpaca) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å | ||||||||||||||||||
Authors | Prevost, M.S. / Barilone, N. / Dejean de la Batie, G. / Pons, S. / Ayme, G. / England, P. / Gielen, M. / Bontems, F. / Pehau-Arnaudet, G. / Maskos, U. ...Prevost, M.S. / 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, P.-J. | ||||||||||||||||||
Funding support | European Union, France, 5items
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Citation | Journal: Nat Commun / Year: 2023 Title: An original potentiating mechanism revealed by the cryo-EM structures of the human α7 nicotinic receptor in complex with nanobodies. Authors: Marie S Prevost / Nathalie Barilone / Gabrielle Dejean de la Bâtie / Stéphanie Pons / Gabriel Ayme / Patrick England / Marc Gielen / François Bontems / Gérard Pehau-Arnaudet / Uwe Maskos ...Authors: Marie S Prevost / Nathalie Barilone / Gabrielle Dejean de la Bâtie / Stéphanie Pons / Gabriel Ayme / Patrick England / Marc Gielen / François Bontems / Gérard Pehau-Arnaudet / Uwe Maskos / Pierre Lafaye / Pierre-Jean Corringer / Abstract: The human α7 nicotinic receptor is a pentameric channel mediating cellular and neuronal communication. It has attracted considerable interest in designing ligands for the treatment of neurological ...The human α7 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 α7 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. | ||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ci2.cif.gz | 558.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ci2.ent.gz | 385.3 KB | Display | PDB format |
PDBx/mmJSON format | 8ci2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ci2_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 8ci2_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8ci2_validation.xml.gz | 48.8 KB | Display | |
Data in CIF | 8ci2_validation.cif.gz | 69.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ci/8ci2 ftp://data.pdbj.org/pub/pdb/validation_reports/ci/8ci2 | HTTPS FTP |
-Related structure data
Related structure data | 16666MC 8c9xC 8cauC 8ce4C 8ci1C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 44050.949 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CHRNA7, NACHRA7 / Production host: Homo sapiens (human) / References: UniProt: P36544 #2: Antibody | Mass: 15826.398 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vicugna pacos (alpaca) / Production host: Homo sapiens (human) #3: Polysaccharide | 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: Sugar | ChemComp-NAG / Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Conc.: 0.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 29644 / Symmetry type: POINT | ||||||||||||||||||||||||
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