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Open data
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Basic information
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Title | Bovine fetal muscle nAChR bound to ACh | |||||||||
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![]() | Bovine muscle nicotinic acetylcholine receptor / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() Highly sodium permeable postsynaptic acetylcholine nicotinic receptors / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / Highly calcium permeable nicotinic acetylcholine receptors / postsynaptic membrane organization / skeletal muscle tissue growth / musculoskeletal movement / neuromuscular synaptic transmission / acetylcholine-gated channel complex / behavioral response to nicotine / muscle cell development ...Highly sodium permeable postsynaptic acetylcholine nicotinic receptors / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / Highly calcium permeable nicotinic acetylcholine receptors / postsynaptic membrane organization / skeletal muscle tissue growth / musculoskeletal movement / neuromuscular synaptic transmission / acetylcholine-gated channel complex / behavioral response to nicotine / muscle cell development / acetylcholine receptor activity / nervous system process / synaptic transmission, cholinergic / acetylcholine binding / acetylcholine-gated monoatomic cation-selective channel activity / acetylcholine receptor signaling pathway / postsynaptic specialization membrane / channel activity / neuromuscular junction development / muscle cell cellular homeostasis / monoatomic cation transport / membrane depolarization / skeletal muscle contraction / neuronal action potential / muscle contraction / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / response to nicotine / neuromuscular junction / neuron cellular homeostasis / postsynaptic membrane / neuron projection / synapse / cell surface / signal transduction / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.45 Å | |||||||||
![]() | Li H / Hibbs RE | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural switch in acetylcholine receptors in developing muscle. Authors: Huanhuan Li / Jinfeng Teng / Ryan E Hibbs / ![]() Abstract: During development, motor neurons originating in the brainstem and spinal cord form elaborate synapses with skeletal muscle fibres. These neurons release acetylcholine (ACh), which binds to nicotinic ...During development, motor neurons originating in the brainstem and spinal cord form elaborate synapses with skeletal muscle fibres. These neurons release acetylcholine (ACh), which binds to nicotinic ACh receptors (AChRs) on the muscle, initiating contraction. Two types of AChR are present in developing muscle cells, and their differential expression serves as a hallmark of neuromuscular synapse maturation. The structural principles underlying the switch from fetal to adult muscle receptors are unknown. Here, we present high-resolution structures of both fetal and adult muscle nicotinic AChRs, isolated from bovine skeletal muscle in developmental transition. These structures, obtained in the absence and presence of ACh, provide a structural context for understanding how fetal versus adult receptor isoforms are tuned for synapse development versus the all-or-none signalling required for high-fidelity skeletal muscle contraction. We find that ACh affinity differences are driven by binding site access, channel conductance is tuned by widespread surface electrostatics and open duration changes result from intrasubunit interactions and structural flexibility. The structures further reveal pathogenic mechanisms underlying congenital myasthenic syndromes. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 226.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.7 KB 22.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.2 KB | Display | ![]() |
Images | ![]() | 42.6 KB | ||
Filedesc metadata | ![]() | 7 KB | ||
Others | ![]() ![]() ![]() ![]() | 206.6 MB 118.7 MB 222.8 MB 222.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9avuMC ![]() 9avvC ![]() 9awjC ![]() 9awkC 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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Annotation | sharp | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.935 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: emhancer
File | emd_43923_additional_1.map | ||||||||||||
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Annotation | emhancer | ||||||||||||
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-Additional map: unsharp
File | emd_43923_additional_2.map | ||||||||||||
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Annotation | unsharp | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: fetal desen halfmapA
File | emd_43923_half_map_1.map | ||||||||||||
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Annotation | fetal_desen_halfmapA | ||||||||||||
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Density Histograms |
-Half map: fetal desen halfmapB
File | emd_43923_half_map_2.map | ||||||||||||
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Annotation | fetal_desen_halfmapB | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Bovine muscle nicotinic acetylcholine receptor
Entire | Name: Bovine muscle nicotinic acetylcholine receptor |
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Components |
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-Supramolecule #1: Bovine muscle nicotinic acetylcholine receptor
Supramolecule | Name: Bovine muscle nicotinic acetylcholine receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Acetylcholine receptor subunit alpha
Macromolecule | Name: Acetylcholine receptor subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 49.949828 KDa |
Sequence | String: SEHETRLVAK LFEDYNSVVR PVEDHRQAVE VTVGLQLIQL INVDEVNQIV TTNVRLKQQW VDYNLKWNPD DYGGVKKIHI PSEKIWRPD LVLYNNADGD FAIVKFTKVL LDYTGHITWT PPAIFKSYCE IIVTHFPFDE QNCSMKLGTW TYDGSVVVIN P ESDQPDLS ...String: SEHETRLVAK LFEDYNSVVR PVEDHRQAVE VTVGLQLIQL INVDEVNQIV TTNVRLKQQW VDYNLKWNPD DYGGVKKIHI PSEKIWRPD LVLYNNADGD FAIVKFTKVL LDYTGHITWT PPAIFKSYCE IIVTHFPFDE QNCSMKLGTW TYDGSVVVIN P ESDQPDLS NFMESGEWVI KESRGWKHWV FYACCPSTPY LDITYHFVMQ RLPLYFIVNV IIPCLLFSFL TGLVFYLPTD SG EKMTLSI SVLLSLTVFL LVIVELIPST SSAVPLIGKY MLFTMVFVIA SIIITVIVIN THHRSPSTHV MPEWVRKVFI DTI PNIMFF STMKRPSREK QDKKIFTEDI DISDISGKPG PPPMGFHSPL IKHPEVKSAI EGIKYIAETM KSDQESNNAA EEWK YVAMV MDHILLAVFM LVCIIGTLAV FAGRLIELNQ QG UniProtKB: Acetylcholine receptor subunit alpha |
-Macromolecule #2: Acetylcholine receptor subunit beta
Macromolecule | Name: Acetylcholine receptor subunit beta / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 55.111832 KDa |
Sequence | String: SEAEGRLREK LFSGYDSTVR PAREVGDRVW VSIGLTLAQL ISLNEKDEEM STKVYLDLEW TDYRLSWDPE EHEGIDSLRI SAESVWLPD VVLLNNNDGN FDVALDINVV VSSDGSMRWQ PPGIYRSSCS IQVTYFPFDW QNCTMVFSSY SYDSSEVSLQ T GLSPEGQE ...String: SEAEGRLREK LFSGYDSTVR PAREVGDRVW VSIGLTLAQL ISLNEKDEEM STKVYLDLEW TDYRLSWDPE EHEGIDSLRI SAESVWLPD VVLLNNNDGN FDVALDINVV VSSDGSMRWQ PPGIYRSSCS IQVTYFPFDW QNCTMVFSSY SYDSSEVSLQ T GLSPEGQE RQEVYIHEGT FIENGQWEII HKPSRLIQPS VDPRGGGEGR REEVTFYLII RRKPLFYLVN VIAPCILITL LA IFVFYLP PDAGEKMGLS IFALLTLTVF LLLLADKVPE TSLSVPIIIK YLMFTMVLVT FSVILSVVVL NLHHRSPHTH QMP LWVRQI FIHKLPLYLG LKRPKPERDQ MQEPPSIAPR DSPGSGWGRG TDEYFIRKPP NDFLFPKPNR FQPELSAPDL RRFI DGPNR AVGLPPELRE VVSSISYIAR QLQEQEDHDV LKEDWQFVAM VVDRLFLWTF IIFTSVGTLV IFLDATYHLP PADPF P UniProtKB: Acetylcholine receptor subunit beta |
-Macromolecule #3: Acetylcholine receptor subunit delta
Macromolecule | Name: Acetylcholine receptor subunit delta / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 56.543926 KDa |
Sequence | String: LNEEERLIRH LFEEKAYNKE LRPAAHKESV EISLALTLSN LISLKEVEET LTTNVWIEQG WTDSRLQWDA EDFGNISVLR LPADMVWLP EIVLENNNDG SFQISYSCNV LIYPSGSVYW LPPAIFRSSC PISVTYFPFD WQNCSLKFSS LKYTTKEITL S LKQAEEDG ...String: LNEEERLIRH LFEEKAYNKE LRPAAHKESV EISLALTLSN LISLKEVEET LTTNVWIEQG WTDSRLQWDA EDFGNISVLR LPADMVWLP EIVLENNNDG SFQISYSCNV LIYPSGSVYW LPPAIFRSSC PISVTYFPFD WQNCSLKFSS LKYTTKEITL S LKQAEEDG RSYPVEWIII DPEGFTENGE WEIVHRPARV NVDPSVPLDS PNRQDVTFYL IIRRKPLFYV INILVPCVLI SF MINLVFY LPADCGEKTS MAISVLLAQS VFLLLISKRL PATSMAIPLI GKFLLFGMVL VTMVVVICVI VLNIHFRTPS THV LSEPVK KLFLETLPEI LHMSRPAEDG PSPGTLIRRS SSLGYISKAE EYFSLKSRSD LMFEKQSERH GLARRLTTAR RPPA GSEQA QQELFSELKP AVDGANFIVN HMKDQNNYNE EKDCWNRVAR TVDRLCLFVV TPIMVVGTAW IFLQGAYNQP PPQPF PGDP FSYLEKDKRF I UniProtKB: Acetylcholine receptor subunit delta |
-Macromolecule #4: Acetylcholine receptor subunit gamma
Macromolecule | Name: Acetylcholine receptor subunit gamma / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 55.99468 KDa |
Sequence | String: RNQEERLLGD LMQGYNPHLR PAEHDSDVVN VSLKLTLTNL ISLNEREEAL TTNVWIEMQW CDYRLRWDPR DYGGLWVLRV PSTMVWRPD IVLENNVDGV FEVALYCNVL VSPDGCVYWL PPAIFRSSCP VSVTFFPFDW QNCSLIFQSQ TYSTNEINLQ L SQEDGQTI ...String: RNQEERLLGD LMQGYNPHLR PAEHDSDVVN VSLKLTLTNL ISLNEREEAL TTNVWIEMQW CDYRLRWDPR DYGGLWVLRV PSTMVWRPD IVLENNVDGV FEVALYCNVL VSPDGCVYWL PPAIFRSSCP VSVTFFPFDW QNCSLIFQSQ TYSTNEINLQ L SQEDGQTI EWIFIDPEAF TENGEWAIRH RPAKMLLDEA APAEEAGHQK VVFYLLIQRK PLFYVINIIA PCVLISSVAI LI YFLPAKA GGQKCTVAIN VLLAQTVFLF LVAKKVPETS QAVPLISKYL TFLLVVTILI VVNAVVVLNV SLRSPHTHSM ARG VRKVFL RLLPQLLRMH VRPLAPVAVQ DAHPRLQNGS SSGWPITAGE EVALCLPRSE LLFRQRQRNG LVRAALEKLE KGPE SGQSP EWCGSLKQAA PAIQACVEAC NLIARARHQQ THFDSGNKEW FLVGRVLDRV CFLAMLSLFV CGTAGIFLMA HYNRV PALP FPGDPRSYLP SSD UniProtKB: Acetylcholine receptor subunit gamma |
-Macromolecule #10: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 10 / Number of copies: 2 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-Macromolecule #11: ACETYLCHOLINE
Macromolecule | Name: ACETYLCHOLINE / type: ligand / ID: 11 / Number of copies: 2 / Formula: ACH |
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Molecular weight | Theoretical: 146.207 Da |
Chemical component information | ![]() ChemComp-ACH: |
-Macromolecule #12: water
Macromolecule | Name: water / type: ligand / ID: 12 / Number of copies: 5 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-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: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.6 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | Chain - Source name: Other / Chain - Initial model type: experimental model / Details: cryosparc ab initial model |
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Refinement | Space: REAL / Protocol: AB INITIO MODEL |
Output model | ![]() PDB-9avu: |