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- EMDB-22892: SARS-CoV-2 Spike Glycoprotein with two ACE2 Bound -

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Basic information

Entry
Database: EMDB / ID: EMD-22892
TitleSARS-CoV-2 Spike Glycoprotein with two ACE2 Bound
Map data
SampleSARS-CoV-2 Spike Glycoprotein with two ACE2 Bound:
Spike glycoproteinSpike protein / Angiotensin-converting enzyme 2 / ligand
Function / homology
Function and homology information


positive regulation of amino acid transport / positive regulation of L-proline import across plasma membrane / angiotensin-converting enzyme 2 / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / tryptophan transport / angiotensin-mediated drinking behavior / positive regulation of cardiac muscle contraction / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / peptidyl-dipeptidase activity ...positive regulation of amino acid transport / positive regulation of L-proline import across plasma membrane / angiotensin-converting enzyme 2 / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / tryptophan transport / angiotensin-mediated drinking behavior / positive regulation of cardiac muscle contraction / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / peptidyl-dipeptidase activity / regulation of cardiac conduction / regulation of vasoconstriction / blood vessel diameter maintenance / angiotensin maturation / Attachment and Entry / Metabolism of Angiotensinogen to Angiotensins / carboxypeptidase activity / metallocarboxypeptidase activity / brush border membrane / regulation of cytokine production / negative regulation of signaling receptor activity / regulation of transmembrane transporter activity / cilium / metallopeptidase activity / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of reactive oxygen species metabolic process / Attachment and Entry / virus receptor activity / receptor-mediated virion attachment to host cell / regulation of cell population proliferation / Potential therapeutics for SARS / endoplasmic reticulum-Golgi intermediate compartment / regulation of inflammatory response / host cell surface receptor binding / endocytosis involved in viral entry into host cell / endocytic vesicle membrane / endopeptidase activity / apical plasma membrane / fusion of virus membrane with host plasma membrane / suppression by virus of host type I interferon-mediated signaling pathway / fusion of virus membrane with host endosome membrane / viral entry into host cell / viral envelope / membrane raft / proteolysis / endoplasmic reticulum lumen / host cell plasma membrane / virion membrane / cell surface / extracellular space / extracellular exosome / zinc ion binding / integral component of membrane / extracellular region / identical protein binding / plasma membrane
Similarity search - Function
Collectrin domain / Renal amino acid transporter / Peptidase M2, peptidyl-dipeptidase A / Angiotensin-converting enzyme / Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Neutral zinc metallopeptidases, zinc-binding region signature. / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily ...Collectrin domain / Renal amino acid transporter / Peptidase M2, peptidyl-dipeptidase A / Angiotensin-converting enzyme / Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Neutral zinc metallopeptidases, zinc-binding region signature. / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein, betacoronavirus / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike receptor binding domain superfamily, coronavirus / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal
Similarity search - Domain/homology
Spike glycoprotein / Angiotensin-converting enzyme 2
Similarity search - Component
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsZhang J / Xiao TS / Cai YF / Chen B
Funding support United States, 4 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI147884 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI147884 01A1S1 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI141002 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI127193 United States
CitationJournal: bioRxiv / Year: 2020
Title: A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro.
Authors: Tianshu Xiao / Jianming Lu / Jun Zhang / Rebecca I Johnson / Lindsay G A McKay / Nadia Storm / Christy L Lavine / Hanqin Peng / Yongfei Cai / Sophia Rits-Volloch / Shen Lu / Brian D Quinlan ...Authors: Tianshu Xiao / Jianming Lu / Jun Zhang / Rebecca I Johnson / Lindsay G A McKay / Nadia Storm / Christy L Lavine / Hanqin Peng / Yongfei Cai / Sophia Rits-Volloch / Shen Lu / Brian D Quinlan / Michael Farzan / Michael S Seaman / Anthony Griffiths / Bing Chen
Abstract: Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the ...Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
History
DepositionOct 25, 2020-
Header (metadata) releaseNov 11, 2020-
Map releaseNov 11, 2020-
UpdateFeb 24, 2021-
Current statusFeb 24, 2021Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.009
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 0.009
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7kj3
  • Surface level: 0.009
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_22892.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 480 pix.
= 396. Å
0.83 Å/pix.
x 480 pix.
= 396. Å
0.83 Å/pix.
x 480 pix.
= 396. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.825 Å
Density
Contour LevelBy AUTHOR: 0.005 / Movie #1: 0.009
Minimum - Maximum-0.043232217 - 0.07744784
Average (Standard dev.)1.9145828e-05 (±0.0016862393)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 396.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.8250.8250.825
M x/y/z480480480
origin x/y/z0.0000.0000.000
length x/y/z396.000396.000396.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS480480480
D min/max/mean-0.0430.0770.000

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Supplemental data

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Sample components

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Entire SARS-CoV-2 Spike Glycoprotein with two ACE2 Bound

EntireName: SARS-CoV-2 Spike Glycoprotein with two ACE2 Bound / Details: SARS-CoV-2 Spike Glycoprotein with two ACE2 Bound / Number of Components: 4

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Component #1: protein, SARS-CoV-2 Spike Glycoprotein with two ACE2 Bound

ProteinName: SARS-CoV-2 Spike Glycoprotein with two ACE2 Bound / Details: SARS-CoV-2 Spike Glycoprotein with two ACE2 Bound / Recombinant expression: No
MassTheoretical: 540 MDa
SourceSpecies: Severe acute respiratory syndrome coronavirus 2
Source (engineered)Expression System: Homo sapiens (human)

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Component #2: protein, Spike glycoprotein

ProteinName: Spike glycoproteinSpike protein / Number of Copies: 3 / Recombinant expression: No
MassTheoretical: 136.559938 kDa
SourceSpecies: Severe acute respiratory syndrome coronavirus 2
Source (engineered)Expression System: Homo sapiens (human)

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Component #3: protein, Angiotensin-converting enzyme 2

ProteinName: Angiotensin-converting enzyme 2 / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 71.024711 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human)

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Component #4: ligand, 2-acetamido-2-deoxy-beta-D-glucopyranose

LigandName: 2-acetamido-2-deoxy-beta-D-glucopyranose / Number of Copies: 40 / Recombinant expression: No
MassTheoretical: 0.221208 kDa

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Experimental details

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Sample preparation

SpecimenSpecimen State: Particle / Method: cryo EM
Sample solutionSpecimen conc.: 1 mg/mL / pH: 7.5
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen Name: ETHANE / Temperature: 277.15 K / Humidity: 100 %

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron Source: FIELD EMISSION GUN / Accelerating Voltage: 300 kV / Electron Dose: 50.05 e/Å2 / Illumination Mode: FLOOD BEAM
LensImaging Mode: BRIGHT FIELD
Specimen HolderModel: OTHER
CameraDetector: OTHER

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Image processing

ProcessingMethod: single particle reconstruction / Number of Projections: 13515
3D reconstructionSoftware: RELION / Resolution: 3.7 Å / Resolution Method: FSC 0.143 CUT-OFF

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Atomic model buiding

Modeling #1Input PDB model: 6VYB, 6M17
Chain ID: A, B
Output model

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