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Yorodumi- EMDB-28576: Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28576 | |||||||||
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Title | Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with rocuronium, resting-like state | |||||||||
Map data | ||||||||||
Sample |
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Keywords | acetylcholine receptor / nicotinic receptor / Torpedo / Cys-loop receptor / ion channel / muscle-type nicotinic receptor / TRANSPORT PROTEIN-INHIBITOR complex / Neuromuscular Blocker / Inhibitor | |||||||||
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) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Goswami U / Rahman MM / Teng J / Hibbs RE | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural interplay of anesthetics and paralytics on muscle nicotinic receptors. Authors: Umang Goswami / Md Mahfuzur Rahman / Jinfeng Teng / Ryan E Hibbs / Abstract: General anesthetics and neuromuscular blockers are used together during surgery to stabilize patients in an unconscious state. Anesthetics act mainly by potentiating inhibitory ion channels and ...General anesthetics and neuromuscular blockers are used together during surgery to stabilize patients in an unconscious state. Anesthetics act mainly by potentiating inhibitory ion channels and inhibiting excitatory ion channels, with the net effect of dampening nervous system excitability. Neuromuscular blockers act by antagonizing nicotinic acetylcholine receptors at the motor endplate; these excitatory ligand-gated ion channels are also inhibited by general anesthetics. The mechanisms by which anesthetics and neuromuscular blockers inhibit nicotinic receptors are poorly understood but underlie safe and effective surgeries. Here we took a direct structural approach to define how a commonly used anesthetic and two neuromuscular blockers act on a muscle-type nicotinic receptor. We discover that the intravenous anesthetic etomidate binds at an intrasubunit site in the transmembrane domain and stabilizes a non-conducting, desensitized-like state of the channel. The depolarizing neuromuscular blocker succinylcholine also stabilizes a desensitized channel but does so through binding to the classical neurotransmitter site. Rocuronium binds in this same neurotransmitter site but locks the receptor in a resting, non-conducting state. Together, this study reveals a structural mechanism for how general anesthetics work on excitatory nicotinic receptors and further rationalizes clinical observations in how general anesthetics and neuromuscular blockers interact. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28576.map.gz | 8.6 MB | EMDB map data format | |
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Header (meta data) | emd-28576-v30.xml emd-28576.xml | 18.8 KB 18.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_28576_fsc.xml | 10.2 KB | Display | FSC data file |
Images | emd_28576.png | 42.5 KB | ||
Others | emd_28576_half_map_1.map.gz emd_28576_half_map_2.map.gz | 71.2 MB 71.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28576 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28576 | HTTPS FTP |
-Validation report
Summary document | emd_28576_validation.pdf.gz | 791.5 KB | Display | EMDB validaton report |
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Full document | emd_28576_full_validation.pdf.gz | 791 KB | Display | |
Data in XML | emd_28576_validation.xml.gz | 17.5 KB | Display | |
Data in CIF | emd_28576_validation.cif.gz | 22.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28576 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28576 | HTTPS FTP |
-Related structure data
Related structure data | 8eskMC 8f2sC 8f6yC 8f6zC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_28576.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.0694 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_28576_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_28576_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in ...
Entire | Name: Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with rocuronium, resting-like state |
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Components |
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-Supramolecule #1: Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in ...
Supramolecule | Name: Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with rocuronium, resting-like state 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 (Pacific electric ray) |
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 #9: rocuronium
Macromolecule | Name: rocuronium / type: ligand / ID: 9 / Number of copies: 2 / Formula: RBR |
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Molecular weight | Theoretical: 529.774 Da |
Chemical component information | ChemComp-RBR: |
-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: 8 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ChemComp-POV: |
-Macromolecule #11: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 11 / Number of copies: 3 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Macromolecule #12: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 12 / Number of copies: 3 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 0.5 µm / Nominal defocus min: 2.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |