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Open data
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Basic information
Entry | Database: PDB / ID: 8hxa | ||||||
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Title | Cryo-EM structure of MPXV M2 in complex with human B7.1 | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / M2 / complex / immune evasion / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | ![]() negative regulation of T cell mediated immunity / positive regulation of T-helper 1 cell differentiation / protein complex involved in cell adhesion / positive regulation of signal transduction / CD28 co-stimulation / positive regulation of granulocyte macrophage colony-stimulating factor production / CD28 dependent Vav1 pathway / CTLA4 inhibitory signaling / Interleukin-10 signaling / CD28 dependent PI3K/Akt signaling ...negative regulation of T cell mediated immunity / positive regulation of T-helper 1 cell differentiation / protein complex involved in cell adhesion / positive regulation of signal transduction / CD28 co-stimulation / positive regulation of granulocyte macrophage colony-stimulating factor production / CD28 dependent Vav1 pathway / CTLA4 inhibitory signaling / Interleukin-10 signaling / CD28 dependent PI3K/Akt signaling / coreceptor activity / positive regulation of T cell proliferation / T cell costimulation / T cell activation / positive regulation of interleukin-2 production / Constitutive Signaling by Aberrant PI3K in Cancer / positive regulation of peptidyl-tyrosine phosphorylation / PIP3 activates AKT signaling / virus receptor activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / cell surface receptor signaling pathway / receptor ligand activity / intracellular signal transduction / immune response / external side of plasma membrane / positive regulation of DNA-templated transcription / cell surface / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.04 Å | ||||||
![]() | Wang, Y. / Yang, S. / Zhao, H. / Deng, Z. | ||||||
Funding support | 1items
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![]() | ![]() Title: Structural and functional insights into the modulation of T cell costimulation by monkeypox virus protein M2. Authors: Shangyu Yang / Yong Wang / Feiyang Yu / Rao Cheng / Yiwei Zhang / Dan Zhou / Xuanxiu Ren / Zengqin Deng / Haiyan Zhao / ![]() Abstract: The rapid spread of monkeypox in multiple countries has resulted in a global public health threat and has caused international concerns since May 2022. Poxvirus encoded M2 protein is a member of the ...The rapid spread of monkeypox in multiple countries has resulted in a global public health threat and has caused international concerns since May 2022. Poxvirus encoded M2 protein is a member of the poxvirus immune evasion family and plays roles in host immunomodulation via the regulation of innate immune response mediated by the NF-κB pathway and adaptive immune response mediated by B7 ligands. However, the interaction of monkeypox virus (MPXV) M2 with B7 ligands and structural insight into poxviral M2 function have remained elusive. Here we reveal that MPXV M2, co-existing as a hexamer and a heptamer, recognizes human B7.1 and B7.2 (hB7.1/2) with high avidities. The binding of oligomeric MPXV M2 interrupts the interactions of hB7.1/2 with CD28 and CTLA4 and subverts T cell activation mediated by B7.1/2 costimulatory signals. Cryo-EM structures of M2 in complex with hB7.1/2 show that M2 binds to the shallow concave face of hB7.1/2 and displays sterically competition with CD28 and CTLA4 for the binding to hB7.1/2. Our findings provide structural mechanisms of poxviral M2 function and immune evasion deployed by poxviruses. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 369.4 KB | Display | ![]() |
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PDB format | ![]() | 300.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 54.2 KB | Display | |
Data in CIF | ![]() | 77.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 35074MC ![]() 8hxbC ![]() 8hxcC 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: 23285.348 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 22893.967 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-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: M2-hB7.1 / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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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
Microscopy | Model: JEOL CRYO ARM 300 |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 251261 / Symmetry type: POINT | ||||||||||||||||||||||||
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