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Open data
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Basic information
Entry | Database: PDB / ID: 8vgt | ||||||
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Title | Structure of the HKU1 RBD bound to the human TMPRSS2 receptor | ||||||
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![]() | VIRAL PROTEIN / Spike glycoprotein / fusion protein / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / inhibitor | ||||||
Function / homology | ![]() transmembrane protease serine 2 / protein autoprocessing / Attachment and Entry / serine-type peptidase activity / endocytosis involved in viral entry into host cell / viral translation / Induction of Cell-Cell Fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / positive regulation of viral entry into host cell ...transmembrane protease serine 2 / protein autoprocessing / Attachment and Entry / serine-type peptidase activity / endocytosis involved in viral entry into host cell / viral translation / Induction of Cell-Cell Fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / proteolysis / extracellular exosome / extracellular region / nucleoplasm / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||
![]() | Park, Y.J. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler, D. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Human coronavirus HKU1 recognition of the TMPRSS2 host receptor. Authors: Matthew McCallum / Young-Jun Park / Cameron Stewart / Kaitlin R Sprouse / Amin Addetia / Jack Brown / M Alejandra Tortorici / Cecily Gibson / Emily Wong / Margareta Ieven / Amalio Telenti / David Veesler / ![]() ![]() Abstract: The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. The molecular basis of HKU1 binding to ...The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. The molecular basis of HKU1 binding to TMPRSS2 and determinants of host receptor tropism remain elusive. We designed an active human TMPRSS2 construct enabling high-yield recombinant production in human cells of this key therapeutic target. We determined a cryo-electron microscopy structure of the HKU1 RBD bound to human TMPRSS2, providing a blueprint of the interactions supporting viral entry and explaining the specificity for TMPRSS2 among orthologous proteases. We identified TMPRSS2 orthologs from five mammalian orders promoting HKU1 S-mediated entry into cells along with key residues governing host receptor usage. Our data show that the TMPRSS2 binding motif is a site of vulnerability to neutralizing antibodies and suggest that HKU1 uses S conformational masking and glycan shielding to balance immune evasion and receptor engagement. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 134.3 KB | Display | ![]() |
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PDB format | ![]() | 98.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 43224MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 37321.785 Da / Num. of mol.: 1 / Fragment: RBD Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||
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#2: Protein | Mass: 46232.004 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: O15393, transmembrane protease serine 2 | ||
#3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||
#4: Sugar | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: HKU1 RBD bound to the human TMPRSS2 receptor / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 810357 / Symmetry type: POINT |