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Open data
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Basic information
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Title | Cryo-EM structure of alpha1AAR-Nb6 complex bound to tamsulosin | |||||||||
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![]() | GPCR / Nanobody / Antagonist / Complex / MEMBRANE PROTEIN | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.35 Å | |||||||||
![]() | Toyoda Y / Zhu A / Yan C / Kobilka BK / Liu X | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of α-adrenergic receptor activation and recognition by an extracellular nanobody. Authors: Yosuke Toyoda / Angqi Zhu / Fang Kong / Sisi Shan / Jiawei Zhao / Nan Wang / Xiaoou Sun / Linqi Zhang / Chuangye Yan / Brian K Kobilka / Xiangyu Liu / ![]() ![]() ![]() Abstract: The αadrenergic receptor (αAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. αAR is involved in smooth muscle contraction and cognitive ...The αadrenergic receptor (αAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. αAR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human αAR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.9 Å to 3.5 Å. Our active and inactive αAR structures reveal the activation mechanism and distinct ligand binding modes for noradrenaline compared with other adrenergic receptor subtypes. In addition, we identified a nanobody that preferentially binds to the extracellular vestibule of αAR when bound to the selective agonist oxymetazoline. These results should facilitate the design of more selective therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.6 KB 16.6 KB | Display Display | ![]() |
Images | ![]() | 55.7 KB | ||
Others | ![]() ![]() | 59.4 MB 59.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 700.5 KB | Display | ![]() |
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Full document | ![]() | 700 KB | Display | |
Data in XML | ![]() | 12.4 KB | Display | |
Data in CIF | ![]() | 14.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ymjMC ![]() 7ym8C ![]() 7ymhC C: citing same article ( M: atomic model generated by this map |
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Links
EMDB pages | ![]() ![]() |
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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_33930_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33930_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : alpha1AAR-Nb6 complex
Entire | Name: alpha1AAR-Nb6 complex |
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Components |
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-Supramolecule #1: alpha1AAR-Nb6 complex
Supramolecule | Name: alpha1AAR-Nb6 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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-Supramolecule #2: alpha1AAR
Supramolecule | Name: alpha1AAR / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Nb6
Supramolecule | Name: Nb6 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: alpha1A-adrenergic receptor
Macromolecule | Name: alpha1A-adrenergic receptor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 40.80418 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDAMVFLSG QASDSSQCTQ PPAPVQISKA ILLGVILGGL ILFGVLGNIL VILSVACHRH LHSVTHYYI VNLAVADLLL TSTVLPFSAI FEVLGYWAFG RVFCNIWAAV DVLCCTARIW GLCIISIDRY IGVSYPLRYP T IVTQRRGL ...String: MKTIIALSYI FCLVFADYKD DDDAMVFLSG QASDSSQCTQ PPAPVQISKA ILLGVILGGL ILFGVLGNIL VILSVACHRH LHSVTHYYI VNLAVADLLL TSTVLPFSAI FEVLGYWAFG RVFCNIWAAV DVLCCTARIW GLCIISIDRY IGVSYPLRYP T IVTQRRGL MALLCVWALS LVISIGPLFG WRQPAPEDET ICQINEEPGY VLFSALGSFY LPLAIILVMY TLMILRLKSV RL LSGSREK DRNLRRITRL VLIVVGCFVL CWLPFFLVMP IGSFFPDFKP SETVFKIVFW LGYLNSCINP IIYPCSSQEF KKA FQNVLR IQCLCRKQSS KHALGYTLHP PSQAVEGQHH HHHHHH |
-Macromolecule #2: Nb6
Macromolecule | Name: Nb6 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 16.51559 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAMAQVQLQE SGGGLVQAGE SLRLSCAASG TIFRLYDMGW YRRVSGNQRE LVASITSGGS TKYGDSVKG RFTISRDNAK NTVYLQMSSL KPEDTAVYYC NAEYRTGIWE ELLDGWGQGT QVTVSSHHHH HH |
-Macromolecule #3: Tamsulosin
Macromolecule | Name: Tamsulosin / type: ligand / ID: 3 / Number of copies: 1 / Formula: JGX |
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Molecular weight | Theoretical: 408.512 Da |
Chemical component information | ![]() ChemComp-JGX: |
-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: 7.5 |
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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 IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.3 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.35 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 285000 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC |