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- EMDB-40979: Cryo-EM structure of the RBD-ACE2 interface of the SARS-CoV-2 tri... -
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Open data
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Basic information
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Title | Cryo-EM structure of the RBD-ACE2 interface of the SARS-CoV-2 trimeric spike protein bound to ACE2 receptor after local refinement at upRBD conformation | |||||||||
![]() | Cryo-EM Map of the RBD-ACE2 interface of the SARS-CoV-2 trimeric spike protein bound to ACE2 receptor after local refinement | |||||||||
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![]() | Coronavirus / Spike / ACE2 / Mink / PROTEIN BINDING / VIRAL PROTEIN | |||||||||
Function / homology | ![]() Hydrolases; Acting on peptide bonds (peptidases) / peptidyl-dipeptidase activity / carboxypeptidase activity / cilium / metallopeptidase activity / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface ...Hydrolases; Acting on peptide bonds (peptidases) / peptidyl-dipeptidase activity / carboxypeptidase activity / cilium / metallopeptidase activity / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / apical plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / proteolysis / extracellular space / identical protein binding / membrane / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.87 Å | |||||||||
![]() | Ahn HM / Calderon B / Fan X / Gao Y / Horgan N / Zhou B / Liang B | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2. Authors: Hyunjun Ahn / Brenda M Calderon / Xiaoyu Fan / Yunrong Gao / Natalie L Horgan / Nannan Jiang / Dylan S Blohm / Jaber Hossain / Nicole Wedad K Rayyan / Sarah H Osman / Xudong Lin / Michael ...Authors: Hyunjun Ahn / Brenda M Calderon / Xiaoyu Fan / Yunrong Gao / Natalie L Horgan / Nannan Jiang / Dylan S Blohm / Jaber Hossain / Nicole Wedad K Rayyan / Sarah H Osman / Xudong Lin / Michael Currier / John Steel / David E Wentworth / Bin Zhou / Bo Liang / ![]() Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across ...Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink (Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a "down" position, approximately 34° lower than previously reported "up" RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 482.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.2 KB 18.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 16.9 KB | Display | ![]() |
Images | ![]() | 12 KB | ||
Filedesc metadata | ![]() | 6.6 KB | ||
Others | ![]() ![]() | 474.6 MB 474.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8t23MC ![]() 8t20C ![]() 8t21C ![]() 8t22C ![]() 8t25C ![]() 8tazC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Cryo-EM Map of the RBD-ACE2 interface of the SARS-CoV-2 trimeric spike protein bound to ACE2 receptor after local refinement | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.11 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half map of the density of the RBD-ACE2...
File | emd_40979_half_map_1.map | ||||||||||||
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Annotation | Half map of the density of the RBD-ACE2 interface of the SARS-CoV-2 trimeric spike protein bound to ACE2 receptor after local refinement. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map of the density of the RBD-ACE2...
File | emd_40979_half_map_2.map | ||||||||||||
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Annotation | Half map of the density of the RBD-ACE2 interface of the SARS-CoV-2 trimeric spike protein bound to ACE2 receptor after local refinement. | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : mink variant spike RBD-ACE2 interface after local refinement
Entire | Name: mink variant spike RBD-ACE2 interface after local refinement |
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Components |
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-Supramolecule #1: mink variant spike RBD-ACE2 interface after local refinement
Supramolecule | Name: mink variant spike RBD-ACE2 interface after local refinement type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Angiotensin-converting enzyme
Macromolecule | Name: Angiotensin-converting enzyme / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 89.3755 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MLGSSWLLLS LAALTAAQST TEDLAKTFLE KFNYEAEELS YQNSLASWNY NTNITDENIQ KMNIAGAKWS AFYEEESQHA KTYPLEEIQ DPIIKRQLRA LQQSGSSVLS ADKRERLNTI LNAMSTIYST GKACNPNNPQ ECLLLEPGLD DIMENSKDYN E RLWAWEGW ...String: MLGSSWLLLS LAALTAAQST TEDLAKTFLE KFNYEAEELS YQNSLASWNY NTNITDENIQ KMNIAGAKWS AFYEEESQHA KTYPLEEIQ DPIIKRQLRA LQQSGSSVLS ADKRERLNTI LNAMSTIYST GKACNPNNPQ ECLLLEPGLD DIMENSKDYN E RLWAWEGW RSEVGKQLRP LYEEYVALKN EMARANNYED YGDYWRGDYE EEWADGYNYS RNQLIEDVEH TFTQIKPLYE HL HAYVRAK LMDAYPSRIS PTGCLPAHLL GDMWGRFWTN LYPLMVPFGQ KPNIDVTDAM VNQSWDARRI FKEAEKFFVS VGL PNMTEG FWQNSMLTEP GDNRKVVCHP TAWDLGKHDF RIKMCTKVTM DDFLTAHHEM GHIQYDMAYA AQPFLLRNGA NEGF HEAVG EIMSLSAATP NHLKNIGLLP PDFSEDSETD INFLLKQALT IVGTLPFTYM LEKWRWMVFK GEIPKEQWMQ KWWEM KRDI VGVVEPLPHD ETYCDPAALF HVANDYSFIR YYTRTIYQFQ FQEALCQIAK HEGPLYKCDI SNSREAGQKL HEMLSL GRS KPWTFALERV VGAKTMDVRP LLNYFEPLFT WLKEQNRNSF VGWNTDWSPY ADQSIKVRIS LKSALGEKAY EWNDNEM YF FQSSIAYAMR EYFSKVKKQT IPFVDKDVRV SDLKPRISFN FIVTSPENMS DIIPRADVEE AIRKSRGRIN DAFRLDDN S LEFLGIQPTL EPPYQPPVGS GSGSGHHHHH HGSGSGLNDI FEAQKIEWHE UniProtKB: Angiotensin-converting enzyme |
-Macromolecule #2: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.370246 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQ IAPGQTGKIA DYNYKLPDDF TGCVIAWNSN NLDSKVGGNY NYLFRLFRKS NLKPFERDIS TEIYQAGSTP C NGVEGFNC ...String: QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQ IAPGQTGKIA DYNYKLPDDF TGCVIAWNSN NLDSKVGGNY NYLFRLFRKS NLKPFERDIS TEIYQAGSTP C NGVEGFNC YFPLQSYGFQ PTNGVGYQPY RVVVLSFELL HAPATVCGPK UniProtKB: Spike glycoprotein |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1.5 mg/mL | |||||||||
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Buffer | pH: 8 Component:
Details: 20 mM Tris pH 8.0, 200 mM NaCl | |||||||||
Grid | Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 11392 / Average exposure time: 4.0 sec. / Average electron dose: 49.98 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 1.75 µm / Nominal defocus min: 0.75 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |