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- PDB-8th3: Structure of AT118-H Nanobody Antagonist in Complex with the Angi... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8th3 | ||||||||||||||||||||||||
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Title | Structure of AT118-H Nanobody Antagonist in Complex with the Angiotensin II Type I Receptor | ||||||||||||||||||||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() synthetic construct (others) | ||||||||||||||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||||||||||||||
![]() | Skiba, M.A. / Kruse, A.C. | ||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Antibodies expand the scope of angiotensin receptor pharmacology. Authors: Meredith A Skiba / Sarah M Sterling / Shaun Rawson / Shuhao Zhang / Huixin Xu / Haoran Jiang / Genevieve R Nemeth / Morgan S A Gilman / Joseph D Hurley / Pengxiang Shen / Dean P Staus / ...Authors: Meredith A Skiba / Sarah M Sterling / Shaun Rawson / Shuhao Zhang / Huixin Xu / Haoran Jiang / Genevieve R Nemeth / Morgan S A Gilman / Joseph D Hurley / Pengxiang Shen / Dean P Staus / Jihee Kim / Conor McMahon / Maria K Lehtinen / Howard A Rockman / Patrick Barth / Laura M Wingler / Andrew C Kruse / ![]() ![]() Abstract: G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to ...G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue and cellular levels. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized. Here, using protein engineering, pharmacological assays and structural studies, we develop maternally selective heavy-chain-only antibody ('nanobody') antagonists against the angiotensin II type I receptor and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to angiotensin II type I receptor with specific small-molecule antagonists and demonstrate that ligand selectivity can be readily tuned. Our work illustrates that antibody fragments can exhibit rich and evolvable pharmacology, attesting to their potential as next-generation GPCR modulators. | ||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 206.8 KB | Display | ![]() |
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PDB format | ![]() | 124.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 41248MC ![]() 8th4C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 65364.684 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() ![]() Gene: AGTR1, AGTR1A, AGTR1B, AT2R1, AT2R1B, cybC / Cell (production host): Expi293 Tet-R / Production host: ![]() ![]() #2: Antibody | | Mass: 24539.314 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Cell (production host): Expi293 Tet-R / Production host: ![]() ![]() #3: Antibody | | Mass: 23541.164 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Cell (production host): Expi293 Tet-R / Production host: ![]() ![]() #4: Chemical | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: AT118-H Nanobody Antagonist in Complex with the Angiotensin II Type I Receptor BRIL Fusion, Anti-BRIL Fab, and Anti-Fab Nanobody Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 Details: 20 mM HEPES, pH 7.4, 100 mM NaCl, 0.05% GDN, 0.005% CHS |
Specimen | Conc.: 9.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 |
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 64.2 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 6309448 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() | ||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 478571 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 60.2 Å2 | ||||||||||||||||||||||||||||||||
Refine LS restraints |
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