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- EMDB-65599: Cryo-EM structure of the human beta2-adrenergic receptor in compl... -

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Basic information

Entry
Database: EMDB / ID: EMD-65599
TitleCryo-EM structure of the human beta2-adrenergic receptor in complex with a novel antagonist
Map data
Sample
  • Complex: Cryo-EM structure of the human beta2-adereneegic receptor in complex with a novel antagonist
    • Protein or peptide: Beta-2 adrenergic receptor,Endolysin
    • Protein or peptide: Beta2 adrenogic receptor inactive-state stabling nanobody Nb60
  • Ligand: BERBERINE
  • Ligand: water
KeywordsAntagonist / membrane protein / GPCR
Function / homology
Function and homology information


beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / AMPA selective glutamate receptor signaling pathway / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / positive regulation of autophagosome maturation / heat generation / norepinephrine binding / Adrenoceptors / negative regulation of smooth muscle contraction ...beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / AMPA selective glutamate receptor signaling pathway / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / positive regulation of autophagosome maturation / heat generation / norepinephrine binding / Adrenoceptors / negative regulation of smooth muscle contraction / positive regulation of cardiac muscle cell contraction / positive regulation of lipophagy / negative regulation of multicellular organism growth / negative regulation of G protein-coupled receptor signaling pathway / adrenergic receptor signaling pathway / response to psychosocial stress / diet induced thermogenesis / endosome to lysosome transport / positive regulation of cAMP/PKA signal transduction / smooth muscle contraction / negative regulation of cardiac muscle cell apoptotic process / adenylate cyclase binding / potassium channel regulator activity / bone resorption / positive regulation of bone mineralization / viral release from host cell by cytolysis / neuronal dense core vesicle / intercellular bridge / regulation of sodium ion transport / adenylate cyclase-activating adrenergic receptor signaling pathway / peptidoglycan catabolic process / positive regulation of cardiac muscle cell apoptotic process / receptor-mediated endocytosis / brown fat cell differentiation / response to cold / clathrin-coated endocytic vesicle membrane / cellular response to amyloid-beta / cell wall macromolecule catabolic process / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / lysozyme / lysozyme activity / mitotic spindle / Cargo recognition for clathrin-mediated endocytosis / positive regulation of cold-induced thermogenesis / amyloid-beta binding / Clathrin-mediated endocytosis / microtubule cytoskeleton / transcription by RNA polymerase II / G alpha (s) signalling events / host cell cytoplasm / early endosome / positive regulation of MAPK cascade / cell surface receptor signaling pathway / lysosome / signaling receptor complex / defense response to bacterium / endosome / endosome membrane / apical plasma membrane / Ub-specific processing proteases / cilium / ciliary basal body / protein-containing complex binding / Golgi apparatus / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / membrane / identical protein binding / nucleus / plasma membrane
Similarity search - Function
Beta 2 adrenoceptor / Adrenoceptor family / Endolysin T4 type / T4-type lysozyme / : / Glycoside hydrolase, family 24 / Phage lysozyme / Lysozyme domain superfamily / Serpentine type 7TM GPCR chemoreceptor Srsx / Lysozyme-like domain superfamily ...Beta 2 adrenoceptor / Adrenoceptor family / Endolysin T4 type / T4-type lysozyme / : / Glycoside hydrolase, family 24 / Phage lysozyme / Lysozyme domain superfamily / Serpentine type 7TM GPCR chemoreceptor Srsx / Lysozyme-like domain superfamily / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile.
Similarity search - Domain/homology
Endolysin / Beta-2 adrenergic receptor
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.04 Å
AuthorsXu T / Liu X
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Cell Discov / Year: 2026
Title: A negative survival pressure selection system enables GPCR antagonist screening.
Authors: Tao Xu / Qinxin Sun / Shuhao Zhang / Tingzhu Liu / Xiaoou Sun / Xusheng Wang / Bin Lin / Zhongjie Liu / Juan Wang / Guodong He / Xiangyu Liu /
History
DepositionJul 29, 2025-
Header (metadata) releaseJun 10, 2026-
Map releaseJun 10, 2026-
UpdateJun 10, 2026-
Current statusJun 10, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_65599.map.gz / Format: CCP4 / Size: 45.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.81 Å/pix.
x 228 pix.
= 184.224 Å
0.81 Å/pix.
x 228 pix.
= 184.224 Å
0.81 Å/pix.
x 228 pix.
= 184.224 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.808 Å
Density
Contour LevelBy AUTHOR: 0.6
Minimum - Maximum-3.5667663 - 4.994698
Average (Standard dev.)-0.00092352484 (±0.10773398)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions228228228
Spacing228228228
CellA=B=C: 184.224 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_65599_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_65599_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Cryo-EM structure of the human beta2-adereneegic receptor in comp...

EntireName: Cryo-EM structure of the human beta2-adereneegic receptor in complex with a novel antagonist
Components
  • Complex: Cryo-EM structure of the human beta2-adereneegic receptor in complex with a novel antagonist
    • Protein or peptide: Beta-2 adrenergic receptor,Endolysin
    • Protein or peptide: Beta2 adrenogic receptor inactive-state stabling nanobody Nb60
  • Ligand: BERBERINE
  • Ligand: water

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Supramolecule #1: Cryo-EM structure of the human beta2-adereneegic receptor in comp...

SupramoleculeName: Cryo-EM structure of the human beta2-adereneegic receptor in complex with a novel antagonist
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Beta-2 adrenergic receptor,Endolysin

MacromoleculeName: Beta-2 adrenergic receptor,Endolysin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: lysozyme
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 58.532844 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString: MKTIIALSYI FCLVFADYKD DDDAMGQPGN GSAFLLAPNR SHAPDHDVTQ QRDEVWVVGM GIVMSLIVLA IVFGNVLVIT AIAKFERLQ TVTNYFITSL ACADLVMGLA VVPFGAAHIL MKMWTFGNFW CEFWTSIDVL CVTASIETLC VIAVDRYFAI T SPFKYQSL ...String:
MKTIIALSYI FCLVFADYKD DDDAMGQPGN GSAFLLAPNR SHAPDHDVTQ QRDEVWVVGM GIVMSLIVLA IVFGNVLVIT AIAKFERLQ TVTNYFITSL ACADLVMGLA VVPFGAAHIL MKMWTFGNFW CEFWTSIDVL CVTASIETLC VIAVDRYFAI T SPFKYQSL LTKNKARVII LMVWIVSGLT SFLPIQMHWY RATHQEAINC YAEETCCDFF TNQAYAIASS IVSFYVPLVI MV FVYSRVF QEAKRQLNIF EMLRIDEGLR LKIYKDTEGY YTIGIGHLLT KSPSLNAAKS ELDKAIGRNT NGVITKDEAE KLF NQDVDA AVRGILRNAK LKPVYDSLDA VRRAALINMV FQMGETGVAG FTNSLRMLQQ KRWDEAAVNL AKSRWYNQTP NRAK RVITT FRTGTWDAYK FCLKEHKALK TLGIIMGTFT LCWLPFFIVN IVHVIQDNLI RKEVYILLNW IGYVNSGFNP LIYCR SPDF RIAFQELLCL RRSSLKAYGN GYSSNGNTGE QSG

UniProtKB: Beta-2 adrenergic receptor, Endolysin, Beta-2 adrenergic receptor

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Macromolecule #2: Beta2 adrenogic receptor inactive-state stabling nanobody Nb60

MacromoleculeName: Beta2 adrenogic receptor inactive-state stabling nanobody Nb60
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 13.531025 KDa
Recombinant expressionOrganism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
SequenceString:
QVQLQESGGG LVQAGGSLRL SCAASGSIFS LNDMGWYRQA PGKLRELVAA ITSGGSTKYA DSVKGRFTIS RDNAKNTVYL QMNSLKAED TAVYYCNAKV AGTFSIYDYW GQGTQVTVSS HHHHHH

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Macromolecule #3: BERBERINE

MacromoleculeName: BERBERINE / type: ligand / ID: 3 / Number of copies: 1 / Formula: BER
Molecular weightTheoretical: 336.361 Da
Chemical component information

ChemComp-BER:
BERBERINE

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Macromolecule #4: water

MacromoleculeName: water / type: ligand / ID: 4 / Number of copies: 1 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 1.3 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 347166
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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