[English] 日本語
Yorodumi- PDB-7rd1: The Capsid Structure of the ChAdOx1 viral vector/chimpanzee adeno... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7rd1 | ||||||
---|---|---|---|---|---|---|---|
Title | The Capsid Structure of the ChAdOx1 viral vector/chimpanzee adenovirus Y25 | ||||||
Components |
| ||||||
Keywords | VIRUS / Adenovirus / simian adenovirus / chimpanzee adenovirus / vaccine vector / DNA virus / AdV / ChAdV-Y25 / adenovirus Y25 / Y25 / viral vector / ChAdOx1 / chimp Ad / dsDNA virus / icosahedral / chimpanzee adenovirus Y25 / Y-25 / Y 25 / ChAdV | ||||||
Function / homology | Function and homology information hexon binding / viral capsid, decoration / T=25 icosahedral viral capsid / lysis of host organelle involved in viral entry into host cell / viral procapsid / microtubule-dependent intracellular transport of viral material towards nucleus / viral release from host cell / endocytosis involved in viral entry into host cell / viral capsid / host cell cytoplasm ...hexon binding / viral capsid, decoration / T=25 icosahedral viral capsid / lysis of host organelle involved in viral entry into host cell / viral procapsid / microtubule-dependent intracellular transport of viral material towards nucleus / viral release from host cell / endocytosis involved in viral entry into host cell / viral capsid / host cell cytoplasm / symbiont entry into host cell / host cell nucleus / virion attachment to host cell / structural molecule activity Similarity search - Function | ||||||
Biological species | Chimpanzee adenovirus Y25 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.07 Å | ||||||
Authors | Baker, A.T. / Boyd, R.J. / Sarkar, D. / Vermaas, J.V. / Williams, D. / Singharoy, A. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Sci Adv / Year: 2021 Title: ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Authors: Alexander T Baker / Ryan J Boyd / Daipayan Sarkar / Alicia Teijeira-Crespo / Chun Kit Chan / Emily Bates / Kasim Waraich / John Vant / Eric Wilson / Chloe D Truong / Magdalena Lipka-Lloyd / ...Authors: Alexander T Baker / Ryan J Boyd / Daipayan Sarkar / Alicia Teijeira-Crespo / Chun Kit Chan / Emily Bates / Kasim Waraich / John Vant / Eric Wilson / Chloe D Truong / Magdalena Lipka-Lloyd / Petra Fromme / Josh Vermaas / Dewight Williams / LeeAnn Machiesky / Meike Heurich / Bolni M Nagalo / Lynda Coughlan / Scott Umlauf / Po-Lin Chiu / Pierre J Rizkallah / Taylor S Cohen / Alan L Parker / Abhishek Singharoy / Mitesh J Borad / Abstract: Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory ...Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS. #1: Journal: Biorxiv / Year: 2021 Title: The Structure of ChAdOx1/AZD-1222 Reveals Interactions with CAR and PF4 with Implications for Vaccine-induced Immune Thrombotic Thrombocytopenia Authors: Baker, A.T. / Boyd, R.J. / Sarkar, D. / Vant, J. / Crespo, A.T. / Waraich, K. / Truong, C.D. / Bates, E. / Wilson, E. / Chan, C.K. / Lipka-Lloyd, M. / Fromme, P. / Nagalo, M.B. / Heurich, M. ...Authors: Baker, A.T. / Boyd, R.J. / Sarkar, D. / Vant, J. / Crespo, A.T. / Waraich, K. / Truong, C.D. / Bates, E. / Wilson, E. / Chan, C.K. / Lipka-Lloyd, M. / Fromme, P. / Nagalo, M.B. / Heurich, M. / Williams, D. / Chiu, P.L. / Rizkallah, P.J. / Parker, A.L. / Singharoy, A. / Borad, M.J. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7rd1.cif.gz | 3.9 MB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7rd1.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7rd1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rd1_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7rd1_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7rd1_validation.xml.gz | 314.4 KB | Display | |
Data in CIF | 7rd1_validation.cif.gz | 497.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rd/7rd1 ftp://data.pdbj.org/pub/pdb/validation_reports/rd/7rd1 | HTTPS FTP |
-Related structure data
Related structure data | 24408MC 7op2C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | |
EM raw data | EMPIAR-10754 (Title: Cryo TEM single particle dataset of purified ChAdOx1/ADZ-1222 Data size: 1.0 TB Data #1: Raw movies comprising 7RD1 ChAdOx dataset [micrographs - multiframe]) |
Experimental dataset #1 | Data reference: 10.1101/2021.05.19.444882 / Data set type: EMPIAR |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
| x 60
2 |
|
3 |
| x 5
4 |
| x 6
5 |
|
Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
-Protein , 4 types, 29 molecules 0U1V2W3X4Y8ZABCDEFGHIJKLMNOPQ
#1: Protein | Mass: 26299.689 Da / Num. of mol.: 12 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chimpanzee adenovirus Y25 / Gene: L3 / Production host: Homo sapiens (human) / References: UniProt: G9G853 #2: Protein | Mass: 106121.141 Da / Num. of mol.: 12 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chimpanzee adenovirus Y25 / Gene: L3 / Production host: Homo sapiens (human) / References: UniProt: G9G854 #3: Protein | | Mass: 59533.656 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chimpanzee adenovirus Y25 / Gene: L2 / Production host: Homo sapiens (human) / References: UniProt: G9G849 #4: Protein | Mass: 14468.118 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chimpanzee adenovirus Y25 / Gene: IX / Production host: Homo sapiens (human) / References: UniProt: G9G843 |
---|
-Pre-hexon-linking protein ... , 2 types, 3 molecules RST
#5: Protein | Mass: 65954.500 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chimpanzee adenovirus Y25 / Production host: Homo sapiens (human) / References: UniProt: G9G848 |
---|---|
#6: Protein | Mass: 24779.684 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chimpanzee adenovirus Y25 / Gene: L4 / Production host: Homo sapiens (human) / References: UniProt: G9G860 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Chimpanzee adenovirus Y25 / Type: VIRUS Details: Rescued from a bacterial artificial chromosome containing the ChAdOx1 genome and propagated in HEK293 T-Rex cells. Entity ID: all / Source: RECOMBINANT | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Chimpanzee adenovirus Y25 / Strain: ChAdOx1 | ||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Details of virus | Empty: NO / Enveloped: NO / Isolate: SPECIES / Type: VIRION | ||||||||||||||||||||
Natural host | Organism: Pan troglodytes | ||||||||||||||||||||
Virus shell | Name: Icosahedral Capsid / Diameter: 500 nm / Triangulation number (T number): 25 | ||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||
Buffer component |
| ||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Concentrated by centrifugation | ||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil R2/2 | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K Details: Grid was R2/2 UltrAUFoil. Sample was applied and blotted twice before plunging. |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 0.2 sec. / Electron dose: 1.1802 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2875 |
Image scans | Movie frames/image: 40 |
-Processing
EM software |
| ||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 8375 | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.07 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 5748 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |