+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14718 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | SARS CoV Spike protein, Closed C1 conformation | ||||||||||||||||||||||||
Map data | |||||||||||||||||||||||||
Sample |
| ||||||||||||||||||||||||
Function / homology | Function and homology information Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / Attachment and Entry / virion component / endocytosis involved in viral entry into host cell / SARS-CoV-1 activates/modulates innate immune responses / suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion ...Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / Attachment and Entry / virion component / endocytosis involved in viral entry into host cell / SARS-CoV-1 activates/modulates innate immune responses / suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell plasma membrane / virion membrane / membrane / identical protein binding Similarity search - Function | ||||||||||||||||||||||||
Biological species | Severe acute respiratory syndrome-related coronavirus / Tequatrovirus T4 | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.71 Å | ||||||||||||||||||||||||
Authors | Toelzer C / Gupta K / Yadav SKN / Buzas D / Borucu U / Schaffitzel C / Berger I | ||||||||||||||||||||||||
Funding support | United Kingdom, 7 items
| ||||||||||||||||||||||||
Citation | Journal: Sci Adv / Year: 2022 Title: The free fatty acid-binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron. Authors: Christine Toelzer / Kapil Gupta / Sathish K N Yadav / Lorna Hodgson / Maia Kavanagh Williamson / Dora Buzas / Ufuk Borucu / Kyle Powers / Richard Stenner / Kate Vasileiou / Frederic Garzoni ...Authors: Christine Toelzer / Kapil Gupta / Sathish K N Yadav / Lorna Hodgson / Maia Kavanagh Williamson / Dora Buzas / Ufuk Borucu / Kyle Powers / Richard Stenner / Kate Vasileiou / Frederic Garzoni / Daniel Fitzgerald / Christine Payré / Gunjan Gautam / Gérard Lambeau / Andrew D Davidson / Paul Verkade / Martin Frank / Imre Berger / Christiane Schaffitzel / Abstract: As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S ...As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)-binding pocket. FFA binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2, and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold-causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation, while the open, infectious conformation is devoid of LA. Electron tomography of SARS-CoV-2-infected cells reveals that LA treatment inhibits viral replication, resulting in fewer deformed virions. Our results establish FFA binding as a hallmark of pathogenic β-CoV infection and replication, setting the stage for FFA-based antiviral strategies to overcome COVID-19. | ||||||||||||||||||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_14718.map.gz | 6.3 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-14718-v30.xml emd-14718.xml | 20.4 KB 20.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14718_fsc.xml | 7.8 KB | Display | FSC data file |
Images | emd_14718.png | 23.4 KB | ||
Masks | emd_14718_msk_1.map | 40.6 MB | Mask map | |
Others | emd_14718_half_map_1.map.gz emd_14718_half_map_2.map.gz | 31.4 MB 31.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14718 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14718 | HTTPS FTP |
-Related structure data
Related structure data | 7zh2MC 7zh1C 7zh5C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_14718.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_14718_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_14718_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_14718_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : SARS CoV Spike protein, Closed conformation, C1 symmetry
Entire | Name: SARS CoV Spike protein, Closed conformation, C1 symmetry |
---|---|
Components |
|
-Supramolecule #1: SARS CoV Spike protein, Closed conformation, C1 symmetry
Supramolecule | Name: SARS CoV Spike protein, Closed conformation, C1 symmetry type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome-related coronavirus |
Molecular weight | Theoretical: 414 KDa |
-Macromolecule #1: Spike glycoprotein,Fibritin
Macromolecule | Name: Spike glycoprotein,Fibritin / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Tequatrovirus T4 |
Molecular weight | Theoretical: 136.201797 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: SDLDRCTTFD DVQAPNYTQH TSSMRGVYYP DEIFRSDTLY LTQDLFLPFY SNVTGFHTIN HTFDNPVIPF KDGIYFAATE KSNVVRGWV FGSTMNNKSQ SVIIINNSTN VVIRACNFEL CDNPFFAVSK PMGTQTHTMI FDNAFNCTFE YISDAFSLDV S EKSGNFKH ...String: SDLDRCTTFD DVQAPNYTQH TSSMRGVYYP DEIFRSDTLY LTQDLFLPFY SNVTGFHTIN HTFDNPVIPF KDGIYFAATE KSNVVRGWV FGSTMNNKSQ SVIIINNSTN VVIRACNFEL CDNPFFAVSK PMGTQTHTMI FDNAFNCTFE YISDAFSLDV S EKSGNFKH LREFVFKNKD GFLYVYKGYQ PIDVVRDLPS GFNTLKPIFK LPLGINITNF RAILTAFSPA QDTWGTSAAA YF VGYLKPT TFMLKYDENG TITDAVDCSQ NPLAELKCSV KSFEIDKGIY QTSNFRVVPS GDVVRFPNIT NLCPFGEVFN ATK FPSVYA WERKKISNCV ADYSVLYNST FFSTFKCYGV SATKLNDLCF SNVYADSFVV KGDDVRQIAP GQTGVIADYN YKLP DDFMG CVLAWNTRNI DATSTGNYNY KYRYLRHGKL RPFERDISNV PFSPDGKPCT PPALNCYWPL NDYGFYTTTG IGYQP YRVV VLSFELLNAP ATVCGPKLST DLIKNQCVNF NFNGLTGTGV LTPSSKRFQP FQQFGRDVSD FTDSVRDPKT SEILDI SPC SFGGVSVITP GTNASSEVAV LYQDVNCTDV STAIHADQLT PAWRIYSTGN NVFQTQAGCL IGAEHVDTSY ECDIPIG AG ICASYHTVSL LRSTSQKSIV AYTMSLGADS SIAYSNNTIA IPTNFSISIT TEVMPVSMAK TSVDCNMYIC GDSTECAN L LLQYGSFCTQ LNRALSGIAA EQDRNTREVF AQVKQMYKTP TLKYFGGFNF SQILPDPLKP TKRSFIEDLL FNKVTLADA GFMKQYGECL GDINARDLIC AQKFNGLTVL PPLLTDDMIA AYTAALVSGT ATAGWTFGAG AALQIPFAMQ MAYRFNGIGV TQNVLYENQ KQIANQFNKA ISQIQESLTT TSTALGKLQD VVNQNAQALN TLVKQLSSNF GAISSVLNDI LSRLDKVEAE V QIDRLITG RLQSLQTYVT QQLIRAAEIR ASANLAATKM SECVLGQSKR VDFCGKGYHL MSFPQAAPHG VVFLHVTYVP SQ ERNFTTA PAICHEGKAY FPREGVFVFN GTSWFITQRN FFSPQIITTD NTFVSGNCDV VIGIINNTVY DPLQPELDSF KEE LDKYFK NHTSPDVDLG DISGINASVV NIQKEIDRLN EVAKNLNESL IDLQELGKYE QYIKPSGRLV PRGSPGSGYI PEAP RDGQA YVRKDGEWVL LSTFLGHHHH HH |
-Macromolecule #3: LINOLEIC ACID
Macromolecule | Name: LINOLEIC ACID / type: ligand / ID: 3 / Number of copies: 3 / Formula: EIC |
---|---|
Molecular weight | Theoretical: 280.445 Da |
Chemical component information | ChemComp-EIC: |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 27 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.5 mg/mL |
---|---|
Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K |
-Electron microscopy
Microscope | TFS TALOS |
---|---|
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number grids imaged: 1 / Number real images: 6600 / Average exposure time: 12.0 sec. / Average electron dose: 62.65 e/Å2 |