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- EMDB-53356: Human alpha7 nicotinic receptor in complex with the E6 nanobody -

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Basic information

Entry
Database: EMDB / ID: EMD-53356
TitleHuman alpha7 nicotinic receptor in complex with the E6 nanobody
Map data
Sample
  • Complex: Human nicotinic acetylcholine receptor alpha7 in complex with Nanobody E6
    • Protein or peptide: Neuronal acetylcholine receptor subunit alpha-7,CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion
    • Protein or peptide: Nanobody E6
  • Ligand: water
KeywordsNicotinic receptor / Nanobody / MEMBRANE PROTEIN
Function / homology
Function and homology information


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 ...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 / extracellular ligand-gated monoatomic ion channel activity / 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
Nicotinic acetylcholine receptor / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor / Neurotransmitter-gated ion-channel / Neurotransmitter-gated ion-channel ligand-binding domain / Neurotransmitter-gated ion-channel ligand-binding domain superfamily / Neurotransmitter-gated ion-channel ligand binding domain
Similarity search - Domain/homology
CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion / Neuronal acetylcholine receptor subunit alpha-7
Similarity search - Component
Biological speciesHomo sapiens (human) / Vicugna pacos (alpaca)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.16 Å
AuthorsBarilone N / Vangelatou M / Marouf FZ / Dejean de la Batie G / Ayme G / Lafaye P / Corringer P-J / Prevost MS
Funding supportEuropean Union, France, 2 items
OrganizationGrant numberCountry
European Research Council (ERC)788974European Union
Agence Nationale de la Recherche (ANR)ANR-23-CE11-0009-01 France
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: 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.
History
DepositionApr 9, 2025-
Header (metadata) releaseFeb 18, 2026-
Map releaseFeb 18, 2026-
UpdateFeb 18, 2026-
Current statusFeb 18, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_53356.png

Downloads & links

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Map

FileDownload / File: emd_53356.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.65 Å/pix.
x 450 pix.
= 290.25 Å		0.65 Å/pix.
x 450 pix.
= 290.25 Å		0.65 Å/pix.
x 450 pix.
= 290.25 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.645 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.08
Minimum - Maximum-0.19038609 - 0.47082907
Average (Standard dev.)0.00020871157 (±0.012151429)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions450450450
Spacing450450450
CellA=B=C: 290.25 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_53356_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

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Half map: #1

Fileemd_53356_half_map_2.map
Projections & Slices
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Sample components

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Entire : Human nicotinic acetylcholine receptor alpha7 in complex with Nan...

EntireName: Human nicotinic acetylcholine receptor alpha7 in complex with Nanobody E6
Components
  • Complex: Human nicotinic acetylcholine receptor alpha7 in complex with Nanobody E6
    • Protein or peptide: Neuronal acetylcholine receptor subunit alpha-7,CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion
    • Protein or peptide: Nanobody E6
  • Ligand: water

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Supramolecule #1: Human nicotinic acetylcholine receptor alpha7 in complex with Nan...

SupramoleculeName: Human nicotinic acetylcholine receptor alpha7 in complex with Nanobody E6
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 325 KDa

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Macromolecule #1: Neuronal acetylcholine receptor subunit alpha-7,CHRNA7 (exons 5-1...

MacromoleculeName: Neuronal acetylcholine receptor subunit alpha-7,CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion
type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 42.83766 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 VEAVSKDFA

UniProtKB: Neuronal acetylcholine receptor subunit alpha-7, CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion

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Macromolecule #2: Nanobody E6

MacromoleculeName: Nanobody E6 / type: protein_or_peptide / ID: 2 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Vicugna pacos (alpaca)
Molecular weightTheoretical: 17.089727 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
AQLQLVESGG GLVQPGGSLR LSCAASGFTL DYYTIGWFRQ APGKEREGVS CIRGSGGSTN YADSVKGRFT ISRDNAKNTV YLQMNSLKP EDTAVYYCAA DFLSTCSLAG YRYEEVWGQG TLVTVSSAHH SEDPSAAAEQ KLISEEDLNG AAHHHHHHGS

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Macromolecule #6: water

MacromoleculeName: water / type: ligand / ID: 6 / Number of copies: 292 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.7 mg/mL
BufferpH: 7.8
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS TITAN THEMIS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 30.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.75 µm / Nominal defocus min: 0.7000000000000001 µm

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.16 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 445239
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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Atomic model buiding 1

RefinementProtocol: RIGID BODY FIT
Output model

PDB-9qto:
Human alpha7 nicotinic receptor in complex with the E6 nanobody

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