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Yorodumi- EMDB-25207: Cryo-EM structure of Torpedo acetylcholine receptor in complex wi... -
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-Basic information
Entry | Database: EMDB / ID: EMD-25207 | |||||||||
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Title | Cryo-EM structure of Torpedo acetylcholine receptor in complex with d-tubocurarine | |||||||||
Map data | Cryo-EM structure of Torpedo acetylcholine receptor in complex with d-tubocurarine | |||||||||
Sample |
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Function / homology | Function and homology information acetylcholine-gated monoatomic cation-selective channel activity / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / transmembrane signaling receptor activity / postsynaptic membrane / neuron projection Similarity search - Function | |||||||||
Biological species | Tetronarce californica (Pacific electric ray) / Pacific electric ray (Pacific electric ray) / Pacific electric ray, Torpedo californica | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.18 Å | |||||||||
Authors | Rahman MM / Basta T / Teng J / Lee M / Worrell BT / Stowell MHB / Hibbs RE | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2022 Title: Structural mechanism of muscle nicotinic receptor desensitization and block by curare. Authors: Md Mahfuzur Rahman / Tamara Basta / Jinfeng Teng / Myeongseon Lee / Brady T Worrell / Michael H B Stowell / Ryan E Hibbs / Abstract: Binding of the neurotransmitter acetylcholine to its receptors on muscle fibers depolarizes the membrane and thereby triggers muscle contraction. We sought to understand at the level of three- ...Binding of the neurotransmitter acetylcholine to its receptors on muscle fibers depolarizes the membrane and thereby triggers muscle contraction. We sought to understand at the level of three-dimensional structure how agonists and antagonists alter nicotinic acetylcholine receptor conformation. We used the muscle-type receptor from the Torpedo ray to first define the structure of the receptor in a resting, activatable state. We then determined the receptor structure bound to the agonist carbachol, which stabilizes an asymmetric, closed channel desensitized state. We find conformational changes in a peripheral membrane helix are tied to recovery from desensitization. To probe mechanisms of antagonism, we obtained receptor structures with the active component of curare, a poison arrow toxin and precursor to modern muscle relaxants. d-Tubocurarine stabilizes the receptor in a desensitized-like state in the presence and absence of agonist. These findings define the transitions between resting and desensitized states and reveal divergent means by which antagonists block channel activity of the muscle-type nicotinic receptor. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_25207.map.gz | 5.2 MB | EMDB map data format | |
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Header (meta data) | emd-25207-v30.xml emd-25207.xml | 17.8 KB 17.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_25207_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_25207.png | 91.4 KB | ||
Others | emd_25207_additional_1.map.gz | 4.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25207 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25207 | HTTPS FTP |
-Validation report
Summary document | emd_25207_validation.pdf.gz | 362.2 KB | Display | EMDB validaton report |
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Full document | emd_25207_full_validation.pdf.gz | 361.7 KB | Display | |
Data in XML | emd_25207_validation.xml.gz | 11 KB | Display | |
Data in CIF | emd_25207_validation.cif.gz | 14.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25207 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25207 | HTTPS FTP |
-Related structure data
Related structure data | 7smsMC 7smmC 7smqC 7smrC 7smtC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_25207.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM structure of Torpedo acetylcholine receptor in complex with d-tubocurarine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0694 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Unsharpened map
File | emd_25207_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Torpedo acetylcholine receptor in complex with d-tubocurarine
Entire | Name: Torpedo acetylcholine receptor in complex with d-tubocurarine |
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Components |
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-Supramolecule #1: Torpedo acetylcholine receptor in complex with d-tubocurarine
Supramolecule | Name: Torpedo acetylcholine receptor in complex with d-tubocurarine type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Tetronarce californica (Pacific electric ray) |
-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: Pacific electric ray (Pacific electric ray) |
Molecular weight | Theoretical: 50.168164 KDa |
Sequence | String: SEHETRLVAN LLENYNKVIR PVEHHTHFVD ITVGLQLIQL ISVDEVNQIV ETNVRLRQQW IDVRLRWNPA DYGGIKKIRL PSDDVWLPD LVLYNNADGD FAIVHMTKLL LDYTGKIMWT PPAIFKSYCE IIVTHFPFDQ QNCTMKLGIW TYDGTKVSIS P ESDRPDLS ...String: SEHETRLVAN LLENYNKVIR PVEHHTHFVD ITVGLQLIQL ISVDEVNQIV ETNVRLRQQW IDVRLRWNPA DYGGIKKIRL PSDDVWLPD LVLYNNADGD FAIVHMTKLL LDYTGKIMWT PPAIFKSYCE IIVTHFPFDQ QNCTMKLGIW TYDGTKVSIS P ESDRPDLS TFMESGEWVM KDYRGWKHWV YYTCCPDTPY LDITYHFIMQ RIPLYFVVNV IIPCLLFSFL TGLVFYLPTD SG EKMTLSI SVLLSLTVFL LVIVELIPST SSAVPLIGKY MLFTMIFVIS SIIITVVVIN THHRSPSTHT MPQWVRKIFI DTI PNVMFF STMKRASKEK QENKIFADDI DISDISGKQV TGEVIFQTPL IKNPDVKSAI EGVKYIAEHM KSDEESSNAA EEWK YVAMV IDHILLCVFM LICIIGTVSV FAGRLIELSQ EG |
-Macromolecule #2: Acetylcholine receptor subunit delta
Macromolecule | Name: Acetylcholine receptor subunit delta / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Pacific electric ray (Pacific electric ray) |
Molecular weight | Theoretical: 57.625711 KDa |
Sequence | String: VNEEERLIND LLIVNKYNKH VRPVKHNNEV VNIALSLTLS NLISLKETDE TLTSNVWMDH AWYDHRLTWN ASEYSDISIL RLPPELVWI PDIVLQNNND GQYHVAYFCN VLVRPNGYVT WLPPAIFRSS CPINVLYFPF DWQNCSLKFT ALNYDANEIT M DLMTDTID ...String: VNEEERLIND LLIVNKYNKH VRPVKHNNEV VNIALSLTLS NLISLKETDE TLTSNVWMDH AWYDHRLTWN ASEYSDISIL RLPPELVWI PDIVLQNNND GQYHVAYFCN VLVRPNGYVT WLPPAIFRSS CPINVLYFPF DWQNCSLKFT ALNYDANEIT M DLMTDTID GKDYPIEWII IDPEAFTENG EWEIIHKPAK KNIYPDKFPN GTNYQDVTFY LIIRRKPLFY VINFITPCVL IS FLASLAF YLPAESGEKM STAISVLLAQ AVFLLLTSQR LPETALAVPL IGKYLMFIMS LVTGVIVNCG IVLNFHFRTP STH VLSTRV KQIFLEKLPR ILHMSRADES EQPDWQNDLK LRRSSSVGYI SKAQEYFNIK SRSELMFEKQ SERHGLVPRV TPRI GFGNN NENIAASDQL HDEIKSGIDS TNYIVKQIKE KNAYDEEVGN WNLVGQTIDR LSMFIITPVM VLGTIFIFVM GNFNH PPAK PFEGDPFDYS SDHPRCA |
-Macromolecule #3: Acetylcholine receptor subunit beta
Macromolecule | Name: Acetylcholine receptor subunit beta / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Pacific electric ray (Pacific electric ray) |
Molecular weight | Theoretical: 53.731773 KDa |
Sequence | String: SVMEDTLLSV LFETYNPKVR PAQTVGDKVT VRVGLTLTNL LILNEKIEEM TTNVFLNLAW TDYRLQWDPA AYEGIKDLRI PSSDVWQPD IVLMNNNDGS FEITLHVNVL VQHTGAVSWQ PSAIYRSSCT IKVMYFPFDW QNCTMVFKSY TYDTSEVTLQ H ALDAKGER ...String: SVMEDTLLSV LFETYNPKVR PAQTVGDKVT VRVGLTLTNL LILNEKIEEM TTNVFLNLAW TDYRLQWDPA AYEGIKDLRI PSSDVWQPD IVLMNNNDGS FEITLHVNVL VQHTGAVSWQ PSAIYRSSCT IKVMYFPFDW QNCTMVFKSY TYDTSEVTLQ H ALDAKGER EVKEIVINKD AFTENGQWSI EHKPSRKNWR SDDPSYEDVT FYLIIQRKPL FYIVYTIIPC ILISILAILV FY LPPDAGE KMSLSISALL AVTVFLLLLA DKVPETSLSV PIIIRYLMFI MILVAFSVIL SVVVLNLHHR SPNTHTMPNW IRQ IFIETL PPFLWIQRPV TTPSPDSKPT IISRANDEYF IRKPAGDFVC PVDNARVAVQ PERLFSEMKW HLNGLTQPVT LPQD LKEAV EAIKYIAEQL ESASEFDDLK KDWQYVAMVA DRLFLYVFFV ICSIGTFSIF LDASHNVPPD NPFA |
-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: Pacific electric ray, Torpedo californica |
Molecular weight | Theoretical: 56.335684 KDa |
Sequence | String: ENEEGRLIEK LLGDYDKRII PAKTLDHIID VTLKLTLTNL ISLNEKEEAL TTNVWIEIQW NDYRLSWNTS EYEGIDLVRI PSELLWLPD VVLENNVDGQ FEVAYYANVL VYNDGSMYWL PPAIYRSTCP IAVTYFPFDW QNCSLVFRSQ TYNAHEVNLQ L SAEEGEAV ...String: ENEEGRLIEK LLGDYDKRII PAKTLDHIID VTLKLTLTNL ISLNEKEEAL TTNVWIEIQW NDYRLSWNTS EYEGIDLVRI PSELLWLPD VVLENNVDGQ FEVAYYANVL VYNDGSMYWL PPAIYRSTCP IAVTYFPFDW QNCSLVFRSQ TYNAHEVNLQ L SAEEGEAV EWIHIDPEDF TENGEWTIRH RPAKKNYNWQ LTKDDTDFQE IIFFLIIQRK PLFYIINIIA PCVLISSLVV LV YFLPAQA GGQKCTLSIS VLLAQTIFLF LIAQKVPETS LNVPLIGKYL IFVMFVSMLI VMNCVIVLNV SLRTPNTHSL SEK IKHLFL GFLPKYLGMQ LEPSEETPEK PQPRRRSSFG IMIKAEEYIL KKPRSELMFE EQKDRHGLKR VNKMTSDIDI GTTV DLYKD LANFAPEIKS CVEACNFIAK STKEQNDSGS ENENWVLIGK VIDKACFWIA LLLFSIGTLA IFLTGHFNQV PEFPF PGDP RKYVP |
-Macromolecule #8: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 8 / Number of copies: 3 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Macromolecule #9: D-TUBOCURARINE
Macromolecule | Name: D-TUBOCURARINE / type: ligand / ID: 9 / Number of copies: 4 / Formula: TC9 |
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Molecular weight | Theoretical: 610.739 Da |
Chemical component information | ChemComp-TC9: |
-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: 5 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ChemComp-POV: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 35.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |