+Open data
-Basic information
Entry | Database: PDB / ID: 7kdt | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Human Tom70 in complex with SARS CoV2 Orf9b | |||||||||||||||
Components |
| |||||||||||||||
Keywords | VIRAL PROTEIN / Orf9b / Tom70 / mitochondria / virus infection / SARS CoV2 | |||||||||||||||
Function / homology | Function and homology information Translation of Accessory Proteins / TOM complex / outer mitochondrial membrane protein complex / mitochondrion targeting sequence binding / negative regulation of defense response to virus / mitochondrial outer membrane translocase complex / protein insertion into mitochondrial inner membrane / protein import into mitochondrial matrix / negative regulation of cell growth involved in cardiac muscle cell development / positive regulation of autophagosome assembly ...Translation of Accessory Proteins / TOM complex / outer mitochondrial membrane protein complex / mitochondrion targeting sequence binding / negative regulation of defense response to virus / mitochondrial outer membrane translocase complex / protein insertion into mitochondrial inner membrane / protein import into mitochondrial matrix / negative regulation of cell growth involved in cardiac muscle cell development / positive regulation of autophagosome assembly / response to thyroxine / Mitochondrial protein import / protein targeting to mitochondrion / positive regulation of protein targeting to mitochondrion / protein insertion into mitochondrial outer membrane / host cell mitochondrion / protein transmembrane transporter activity / negative regulation of mitochondrial fission / positive regulation of defense response to virus by host / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / PINK1-PRKN Mediated Mitophagy / activation of innate immune response / positive regulation of interferon-beta production / protein sequestering activity / mitochondrial membrane / DDX58/IFIH1-mediated induction of interferon-alpha/beta / cellular response to virus / SARS-CoV-1 activates/modulates innate immune responses / regulation of apoptotic process / mitochondrial outer membrane / molecular adaptor activity / Ub-specific processing proteases / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / SARS-CoV-2 activates/modulates innate and adaptive immune responses / mitochondrion / extracellular exosome / membrane / identical protein binding Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) Severe acute respiratory syndrome coronavirus 2 | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.05 Å | |||||||||||||||
Authors | QCRG Structural Biology Consortium | |||||||||||||||
Funding support | United States, 4items
| |||||||||||||||
Citation | Journal: Science / Year: 2020 Title: Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Authors: David E Gordon / Joseph Hiatt / Mehdi Bouhaddou / Veronica V Rezelj / Svenja Ulferts / Hannes Braberg / Alexander S Jureka / Kirsten Obernier / Jeffrey Z Guo / Jyoti Batra / Robyn M Kaake / ...Authors: David E Gordon / Joseph Hiatt / Mehdi Bouhaddou / Veronica V Rezelj / Svenja Ulferts / Hannes Braberg / Alexander S Jureka / Kirsten Obernier / Jeffrey Z Guo / Jyoti Batra / Robyn M Kaake / Andrew R Weckstein / Tristan W Owens / Meghna Gupta / Sergei Pourmal / Erron W Titus / Merve Cakir / Margaret Soucheray / Michael McGregor / Zeynep Cakir / Gwendolyn Jang / Matthew J O'Meara / Tia A Tummino / Ziyang Zhang / Helene Foussard / Ajda Rojc / Yuan Zhou / Dmitry Kuchenov / Ruth Hüttenhain / Jiewei Xu / Manon Eckhardt / Danielle L Swaney / Jacqueline M Fabius / Manisha Ummadi / Beril Tutuncuoglu / Ujjwal Rathore / Maya Modak / Paige Haas / Kelsey M Haas / Zun Zar Chi Naing / Ernst H Pulido / Ying Shi / Inigo Barrio-Hernandez / Danish Memon / Eirini Petsalaki / Alistair Dunham / Miguel Correa Marrero / David Burke / Cassandra Koh / Thomas Vallet / Jesus A Silvas / Caleigh M Azumaya / Christian Billesbølle / Axel F Brilot / Melody G Campbell / Amy Diallo / Miles Sasha Dickinson / Devan Diwanji / Nadia Herrera / Nick Hoppe / Huong T Kratochvil / Yanxin Liu / Gregory E Merz / Michelle Moritz / Henry C Nguyen / Carlos Nowotny / Cristina Puchades / Alexandrea N Rizo / Ursula Schulze-Gahmen / Amber M Smith / Ming Sun / Iris D Young / Jianhua Zhao / Daniel Asarnow / Justin Biel / Alisa Bowen / Julian R Braxton / Jen Chen / Cynthia M Chio / Un Seng Chio / Ishan Deshpande / Loan Doan / Bryan Faust / Sebastian Flores / Mingliang Jin / Kate Kim / Victor L Lam / Fei Li / Junrui Li / Yen-Li Li / Yang Li / Xi Liu / Megan Lo / Kyle E Lopez / Arthur A Melo / Frank R Moss / Phuong Nguyen / Joana Paulino / Komal Ishwar Pawar / Jessica K Peters / Thomas H Pospiech / Maliheh Safari / Smriti Sangwan / Kaitlin Schaefer / Paul V Thomas / Aye C Thwin / Raphael Trenker / Eric Tse / Tsz Kin Martin Tsui / Feng Wang / Natalie Whitis / Zanlin Yu / Kaihua Zhang / Yang Zhang / Fengbo Zhou / Daniel Saltzberg / / Anthony J Hodder / Amber S Shun-Shion / Daniel M Williams / Kris M White / Romel Rosales / Thomas Kehrer / Lisa Miorin / Elena Moreno / Arvind H Patel / Suzannah Rihn / Mir M Khalid / Albert Vallejo-Gracia / Parinaz Fozouni / Camille R Simoneau / Theodore L Roth / David Wu / Mohd Anisul Karim / Maya Ghoussaini / Ian Dunham / Francesco Berardi / Sebastian Weigang / Maxime Chazal / Jisoo Park / James Logue / Marisa McGrath / Stuart Weston / Robert Haupt / C James Hastie / Matthew Elliott / Fiona Brown / Kerry A Burness / Elaine Reid / Mark Dorward / Clare Johnson / Stuart G Wilkinson / Anna Geyer / Daniel M Giesel / Carla Baillie / Samantha Raggett / Hannah Leech / Rachel Toth / Nicola Goodman / Kathleen C Keough / Abigail L Lind / / Reyna J Klesh / Kafi R Hemphill / Jared Carlson-Stevermer / Jennifer Oki / Kevin Holden / Travis Maures / Katherine S Pollard / Andrej Sali / David A Agard / Yifan Cheng / James S Fraser / Adam Frost / Natalia Jura / Tanja Kortemme / Aashish Manglik / Daniel R Southworth / Robert M Stroud / Dario R Alessi / Paul Davies / Matthew B Frieman / Trey Ideker / Carmen Abate / Nolwenn Jouvenet / Georg Kochs / Brian Shoichet / Melanie Ott / Massimo Palmarini / Kevan M Shokat / Adolfo García-Sastre / Jeremy A Rassen / Robert Grosse / Oren S Rosenberg / Kliment A Verba / Christopher F Basler / Marco Vignuzzi / Andrew A Peden / Pedro Beltrao / Nevan J Krogan / Abstract: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more ...The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study. | |||||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7kdt.cif.gz | 200.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7kdt.ent.gz | 159 KB | Display | PDB format |
PDBx/mmJSON format | 7kdt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kd/7kdt ftp://data.pdbj.org/pub/pdb/validation_reports/kd/7kdt | HTTPS FTP |
---|
-Related structure data
Related structure data | 22829MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 56875.727 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TOMM70, KIAA0719, TOM70, TOMM70A / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: O94826 |
---|---|
#2: Protein | Mass: 10808.636 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: 9b / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P0DTD2 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Orf9b-Tom70 complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||
Source (recombinant) | Organism: Escherichia coli BL21(DE3) (bacteria) | ||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||
Buffer component |
| ||||||||||||||||
Specimen | Conc.: 12.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K Details: Blot for 5 seconds before plunging into liquid ethane |
-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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 105000 X / Alignment procedure: ZEMLIN TABLEAU |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 66 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 1534 |
-Processing
EM software |
| ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Details: Done at the reconstruction stage as is standard for cryoSPARC Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2805121 Details: Template picked based on previous low resolution reconstruction (which was picked with a blob picker) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.05 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 178373 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 3FP3 Accession code: 3FP3 / Source name: PDB / Type: experimental model |