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- EMDB-16665: Human alpha7 nicotinic receptor in complex with the E3 nanobody a... -
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Open data
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Basic information
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Title | Human alpha7 nicotinic receptor in complex with the E3 nanobody and nicotine | ||||||||||||||||||
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![]() | ion channel nanobody Nicotinic acetylcholine receptor / MEMBRANE PROTEIN | ||||||||||||||||||
Function / homology | ![]() sensory processing / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine-gated channel complex / regulation of amyloid fibril formation / short-term memory / positive regulation of CoA-transferase activity / acetylcholine receptor activity / dendritic spine organization ...sensory processing / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine-gated channel complex / regulation of amyloid fibril formation / short-term memory / positive regulation of CoA-transferase activity / acetylcholine receptor activity / dendritic spine organization / chloride channel regulator activity / acetylcholine binding / regulation of amyloid precursor protein catabolic process / acetylcholine-gated monoatomic cation-selective channel activity / 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 / monoatomic ion transmembrane transport / positive regulation of protein metabolic process / positive regulation of long-term synaptic potentiation / synapse organization / response to nicotine / calcium channel activity / memory / cognition / intracellular calcium ion homeostasis / positive regulation of angiogenesis / calcium ion transport / monoatomic ion channel activity / 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 / synapse / positive regulation of cell population proliferation / signal transduction / protein homodimerization activity / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||||||||
![]() | Prevost MS / Barilone N / Dejean de la Batie G / Pons S / Ayme G / England P / Gielen M / Bontems F / Pehau-Arnaudet G / Maskos U ...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 P-J | ||||||||||||||||||
Funding support | European Union, ![]()
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![]() | ![]() 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 80.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.7 KB 17.7 KB | Display Display | ![]() |
Images | ![]() | 42.7 KB | ||
Filedesc metadata | ![]() | 6 KB | ||
Others | ![]() ![]() | 80.9 MB 80.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ci1MC ![]() 8c9xC ![]() 8cauC ![]() 8ce4C ![]() 8ci2C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_16665_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_16665_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : complex of the human alpha7 nicotinic acetylcholine receptor with...
Entire | Name: complex of the human alpha7 nicotinic acetylcholine receptor with the nanobody E3 |
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Components |
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-Supramolecule #1: complex of the human alpha7 nicotinic acetylcholine receptor with...
Supramolecule | Name: complex of the human alpha7 nicotinic acetylcholine receptor with the nanobody E3 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
-Supramolecule #2: human alpha7 nicotinic acetylcholine receptor
Supramolecule | Name: human alpha7 nicotinic acetylcholine receptor / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Nanobody E3
Supramolecule | Name: Nanobody E3 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Neuronal acetylcholine receptor subunit alpha-7
Macromolecule | Name: Neuronal acetylcholine receptor subunit alpha-7 / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 44.050949 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EFQRKLYKEL VKNYNPLERP VANDSQPLTV YFSLSLLQIM DVDEKNQVLT TNIWLQMSWT DHYLQWNVSE YPGVKTVRFP DGQIWKPDI LLYNSADERF DATFHTNVLV NSSGHCQYLP PGIFKSSCYI DVRWFPFDVQ HCKLKFGSWS YGGWSLDLQM Q EADISGYI ...String: EFQRKLYKEL VKNYNPLERP VANDSQPLTV YFSLSLLQIM DVDEKNQVLT TNIWLQMSWT DHYLQWNVSE YPGVKTVRFP DGQIWKPDI LLYNSADERF DATFHTNVLV NSSGHCQYLP PGIFKSSCYI DVRWFPFDVQ HCKLKFGSWS YGGWSLDLQM Q EADISGYI PNGEWDLVGI PGKRSERFYE CCKEPYPDVT FTVTMRRRTL YYGLNLLIPC VLISALALLV FLLPADSGEK IS LGITVLL SLTVFMLLVA EIMPATSDSV PLIAQYFAST MIIVGLSVVV TVIVLQYHHH DPDGGKMPKW TRVILLNWCA WFL RMKRDG VAVCSEWKFA ACVVDRLCLM AFSVFTIICT IGILMSAPNF VEAVSKDFAS AGLTETSQVA PA UniProtKB: Neuronal acetylcholine receptor subunit alpha-7, Neuronal acetylcholine receptor subunit alpha-7 |
-Macromolecule #2: Nanobody E3
Macromolecule | Name: Nanobody E3 / type: protein_or_peptide / ID: 2 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 15.740189 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AVQLQASGGG LVQAGDSLRL SCAASGGTFS HYAVGWFRQA PGKEREFVAA ISWSGRSTSF ANSVKGRFTI SRDSAKNTAY LQMNNLKPE DTAVYCCAPA RFGTGSAARD EYDDCGQGTQ VTVSSAAAEQ KLISEEDLNG AAHHHHHHGS |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 10 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #5: (S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE
Macromolecule | Name: (S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE / type: ligand / ID: 5 / Number of copies: 5 / Formula: NCT |
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Molecular weight | Theoretical: 162.232 Da |
Chemical component information | ![]() ChemComp-NCT: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 114385 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |