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- EMDB-31147: Structure of the alpha2A-adrenergic receptor GoA signaling complex -
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Open data
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Basic information
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Title | Structure of the alpha2A-adrenergic receptor GoA signaling complex | |||||||||
![]() | 3.2 angstrom alpha2A-Go complex bound to norepi | |||||||||
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Function / homology | ![]() negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / phospholipase C-activating adrenergic receptor signaling pathway / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Xu J / Cao S / Liu Z / Du Y | |||||||||
![]() | ![]() Title: Structural insights into ligand recognition, activation, and signaling of the α adrenergic receptor. Authors: Jun Xu / Sheng Cao / Harald Hübner / Dorothée Weikert / Geng Chen / Qiuyuan Lu / Daopeng Yuan / Peter Gmeiner / Zheng Liu / Yang Du / ![]() ![]() Abstract: The α adrenergic receptor (αAR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous ...The α adrenergic receptor (αAR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous neurotransmitters norepinephrine and epinephrine, as well as numerous chemically distinct drugs. However, the molecular mechanisms of drug actions remain poorly understood. Here, we report the cryo-electron microscopy structures of the human αAR-GoA complex bound to norepinephrine and three imidazoline derivatives (brimonidine, dexmedetomidine, and oxymetazoline). Together with mutagenesis and functional data, these structures provide important insights into the molecular basis of ligand recognition, activation, and signaling at the αAR. Further structural analyses uncover different molecular determinants between αAR and βARs for recognition of norepinephrine and key regions that determine the G protein coupling selectivity. Overall, our studies provide a framework for understanding the signal transduction of the adrenergic system at the atomic level, which will facilitate rational structure-based discovery of safer and more effective medications for αAR. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17 KB 17 KB | Display Display | ![]() |
Images | ![]() | 62.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ej0MC ![]() 7ej8C ![]() 7ejaC ![]() 7ejkC 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 | 3.2 angstrom alpha2A-Go complex bound to norepi | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : alpha2A-adrenergic receptor Go signaling complex
Entire | Name: alpha2A-adrenergic receptor Go signaling complex |
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Components |
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-Supramolecule #1: alpha2A-adrenergic receptor Go signaling complex
Supramolecule | Name: alpha2A-adrenergic receptor Go signaling complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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-Supramolecule #2: alpha2A-adrenergic receptor Go signaling complex
Supramolecule | Name: alpha2A-adrenergic receptor Go signaling complex / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3, #5 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() ![]() |
-Supramolecule #3: scFv16
Supramolecule | Name: scFv16 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4 |
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Source (natural) | Organism: ![]() ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Guanine nucleotide-binding protein G(o) subunit alpha
Macromolecule | Name: Guanine nucleotide-binding protein G(o) subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 40.1005 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGCTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG AGESGKSTIV KQMKIIHEDG FSGEDVKQYK PVVYSNTIQS LAAIVRAMD TLGIEYGDKE RKADAKMVCD VVSRMEDTEP FSAELLSAMM RLWGDSGIQE CFNRSREYQL NDSAKYYLDS L DRIGAADY ...String: MGCTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG AGESGKSTIV KQMKIIHEDG FSGEDVKQYK PVVYSNTIQS LAAIVRAMD TLGIEYGDKE RKADAKMVCD VVSRMEDTEP FSAELLSAMM RLWGDSGIQE CFNRSREYQL NDSAKYYLDS L DRIGAADY QPTEQDILRT RVKTTGIVET HFTFKNLHFR LFDVGGQRSE RKKWIHCFED VTAIIFCVAL SGYDQVLHED ET TNRMHES LMLFDSICNN KFFIDTSIIL FLNKKDLFGE KIKKSPLTIC FPEYTGPNTY EDAAAYIQAQ FESKNRSPNK EIY CHMTCA TDTNNIQVVF DAVTDIIIAN NLRGCGLY |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 38.402867 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: HHHHHHGSSG SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLI IWDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR F LDDNQIVT ...String: HHHHHHGSSG SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLI IWDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR F LDDNQIVT SSGDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NA ICFFPNG NAFATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGH DNRVSC LGVTDDGMAV ATGSWDSFLK IWN |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #4: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 32.898781 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFADV QLVESGGGLV QPGGSRKLSC SASGFAFSSF GMHWVRQAPE KGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSEDT AMYYCVRSIY YYGSSPFDFW GQGTTLTVSS G GGGSGGGG ...String: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFADV QLVESGGGLV QPGGSRKLSC SASGFAFSSF GMHWVRQAPE KGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSEDT AMYYCVRSIY YYGSSPFDFW GQGTTLTVSS G GGGSGGGG SGGGGSDIVM TQATSSVPVT PGESVSISCR SSKSLLHSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DR FSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GAGTKLELKG SLEVLFQGPA AAHHHHHHHH |
-Macromolecule #5: Alpha-2A adrenergic receptor
Macromolecule | Name: Alpha-2A adrenergic receptor / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 50.704566 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MFRQEQPLAE GSFAPMGSLQ PDAGNASWNG TEAPGGGARA TPYSLQVTLT LVCLAGLLML LTVFGNVLVI IAVFTSRALK APQNLFLVS LASADILVAT LVIPFSLANE VMGYWYFGKA WCEIYLALDV LFCTSSIVHL CAISLDRYWS ITQAIEYNLK R TPRRIKAI ...String: MFRQEQPLAE GSFAPMGSLQ PDAGNASWNG TEAPGGGARA TPYSLQVTLT LVCLAGLLML LTVFGNVLVI IAVFTSRALK APQNLFLVS LASADILVAT LVIPFSLANE VMGYWYFGKA WCEIYLALDV LFCTSSIVHL CAISLDRYWS ITQAIEYNLK R TPRRIKAI IITVWVISAV ISFPPLISIE KKGGGGGPQP AEPRCEINDQ KWYVISSCIG SFFAPCLIMI LVYVRIYQIA KR RTRVPPS RRGPDAVAAP PGGTERRPNG LGPERSAGPG GAEAEPLPTQ LNGAPGEPAP AGPRDTDALD LEESSSSDHA ERP PGPRRP ERGPRGKGKA RASQVKPGDS LPRRGPGATG IGTPAAGPGE ERVGAAKASR WRGRQNREKR FTFVLAVVIG VFVV CWFPF FFTYTLTAVG CSVPRTLFKF FFWFGYCNSS LNPVIYTIFN HDFRRAFKKI LCRGDRKRIV |
-Macromolecule #6: Noradrenaline
Macromolecule | Name: Noradrenaline / type: ligand / ID: 6 / Number of copies: 1 / Formula: E5E |
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Molecular weight | Theoretical: 170.186 Da |
Chemical component information | ![]() ChemComp-E5E: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Sugar embedding | Material: vitreous ice |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Calibrated defocus max: 2.0 µm / Calibrated defocus min: 0.8 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 56.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Initial angle assignment | Type: RANDOM ASSIGNMENT |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 261073 |