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- PDB-9mao: SARS-CoV-2 spike-Crp5 -

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Basic information

Entry
Database: PDB / ID: 9mao
TitleSARS-CoV-2 spike-Crp5
Components
  • Alpha-defensin 5
  • Spike glycoprotein
KeywordsVIRAL PROTEIN / SARS-CoV-2 / cryo-EM structure / defensin
Function / homology
Function and homology information


Alpha-defensins / Defensins / positive regulation of membrane permeability / disruption of plasma membrane integrity in another organism / pore-forming activity / : / Neutrophil degranulation / secretory granule / positive regulation of interleukin-8 production / midbody ...Alpha-defensins / Defensins / positive regulation of membrane permeability / disruption of plasma membrane integrity in another organism / pore-forming activity / : / Neutrophil degranulation / secretory granule / positive regulation of interleukin-8 production / midbody / symbiont-mediated disruption of host tissue / antimicrobial humoral immune response mediated by antimicrobial peptide / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / Lectin pathway of complement activation / host extracellular region / antibacterial humoral response / symbiont-mediated-mediated suppression of host tetherin activity / killing of cells of another organism / Induction of Cell-Cell Fusion / structural constituent of virion / defense response to Gram-negative bacterium / protein homotetramerization / positive regulation of viral entry into host cell / Initial triggering of complement / membrane fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / entry receptor-mediated virion attachment to host cell / receptor-mediated virion attachment to host cell / defense response to bacterium / defense response to Gram-positive bacterium / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / endocytosis involved in viral entry into host cell / receptor ligand activity / fusion of virus membrane with host plasma membrane / innate immune response / fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell plasma membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / virion membrane / protein homodimerization activity / : / membrane / identical protein binding / plasma membrane
Similarity search - Function
Mammalian defensins signature. / Alpha-defensin, C-terminal / Mammalian defensin / Alpha-defensin propeptide / Alpha-defensin / Defensin propeptide / Defensin propeptide / Beta/alpha-defensin, C-terminal / Defensin/corticostatin family / Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 ...Mammalian defensins signature. / Alpha-defensin, C-terminal / Mammalian defensin / Alpha-defensin propeptide / Alpha-defensin / Defensin propeptide / Defensin propeptide / Beta/alpha-defensin, C-terminal / Defensin/corticostatin family / Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, N-terminal domain superfamily / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Spike glycoprotein, betacoronavirus / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Spike glycoprotein / Alpha-defensin 5
Similarity search - Component
Biological speciesSevere acute respiratory syndrome coronavirus 2
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.09 Å
AuthorsYang, Q.X. / Yang, Y.L.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31970146 China
National Natural Science Foundation of China (NSFC)82030062 China
CitationJournal: Mucosal Immunol / Year: 2026
Title: Enteric α-defensins contribute to intestinal mucosal immunity against SARS-CoV-2 infection.
Authors: Yilin Yang / Qianxi Yang / Xin Huang / Chongbing Liao / Zhenguo Chen / Wuyuan Lu /
Abstract: SARS-CoV-2 primarily targets epithelial cells in the respiratory and intestinal tracts where its cognate receptor ACE2 and obligate processing enzymes furin and TMPRSS2 are richly expressed. However, ...SARS-CoV-2 primarily targets epithelial cells in the respiratory and intestinal tracts where its cognate receptor ACE2 and obligate processing enzymes furin and TMPRSS2 are richly expressed. However, compared with severe inflammation and tissue damage in the lungs of a COVID-19 patient, clinical lesions in the intestine are rare, suggesting an effective intestinal mucosal immunity against SARS-CoV-2 infection. Here, we report that MMP7/hACE2 hybrid mice lacking mature enteric α-defensins or cryptdins were more susceptible to SARS-CoV-2 infection in the intestine than K18-hACE2 transgenic mice. The mouse α-defensin cryptdin-5 (Crp5) displayed potent and broad antiviral activity in vitro and in vivo by two distinct mechanisms, (1) directly targeting the RBD of the spike (S) protein to antagonize its interactions with ACE2, thus blocking viral attachment, membrane fusion and cell-to-cell transmission, and (2) binding to the 630 loop of the S protein to induce its multimerization, thereby impairing proteolytic processing, membrane fusion and, ultimately, viral infectivity. Our findings imply that enteric α-defensins help alleviate, as host protective factors, Covid-19 symptoms in the intestine despite higher ACE2 expression in the gut than in the lungs, and that Crp5 may be developed as a broad-spectrum antiviral for the treatment of coronavirus infection irrespective of virus type and variant.
History
DepositionMar 14, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Aug 12, 2026Provider: repository / Type: Initial release
Revision 1.0Aug 12, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
C: Spike glycoprotein
B: Spike glycoprotein
A: Spike glycoprotein
D: Alpha-defensin 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)436,83243
Polymers428,2054
Non-polymers8,62739
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Spike glycoprotein / S glycoprotein / E2 / Peplomer protein


Mass: 141291.406 Da / Num. of mol.: 3 / Mutation: F817P/A892P/A899P/A942P/K986P/V987P
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Gene: S, 2 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P0DTC2
#2: Protein/peptide Alpha-defensin 5 / Defensin-related cryptdin-5


Mass: 4330.334 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Mus musculus (house mouse) / References: UniProt: P28312
#3: Sugar...
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 39
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6 / Feature type: SUBJECT OF INVESTIGATION
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: SARS-CoV-2 spike-Crp5 Complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.17.1_3660 / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.09 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 42414 / Symmetry type: POINT
RefinementStereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00125305
ELECTRON MICROSCOPYf_angle_d0.39534485
ELECTRON MICROSCOPYf_dihedral_angle_d19.9579010
ELECTRON MICROSCOPYf_chiral_restr0.0414074
ELECTRON MICROSCOPYf_plane_restr0.0034426

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