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- EMDB-35075: Cryo-EM structure of MPXV M2 hexamer in complex with human B7.2 -
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Open data
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Basic information
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Title | Cryo-EM structure of MPXV M2 hexamer in complex with human B7.2 | |||||||||
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![]() | M2 / complex / immune evasion / VIRAL PROTEIN | |||||||||
Function / homology | ![]() positive regulation of lymphotoxin A production / CD40 signaling pathway / positive regulation of T-helper 2 cell differentiation / activation of protein kinase C activity / CD28 co-stimulation / : / CD28 dependent Vav1 pathway / positive regulation of immunoglobulin production / CTLA4 inhibitory signaling / B cell activation ...positive regulation of lymphotoxin A production / CD40 signaling pathway / positive regulation of T-helper 2 cell differentiation / activation of protein kinase C activity / CD28 co-stimulation / : / CD28 dependent Vav1 pathway / positive regulation of immunoglobulin production / CTLA4 inhibitory signaling / B cell activation / positive regulation of interleukin-4 production / Interleukin-10 signaling / CD28 dependent PI3K/Akt signaling / centriolar satellite / coreceptor activity / positive regulation of T cell proliferation / T cell costimulation / T cell activation / positive regulation of interleukin-2 production / positive regulation of non-canonical NF-kappaB signal transduction / Constitutive Signaling by Aberrant PI3K in Cancer / PIP3 activates AKT signaling / virus receptor activity / signaling receptor activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / adaptive immune response / cell surface receptor signaling pathway / receptor ligand activity / immune response / external side of plasma membrane / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / cell surface / extracellular exosome / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
![]() | Wang Y / Yang S / Zhao H / Deng Z | |||||||||
Funding support | 1 items
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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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 117.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.1 KB 14.1 KB | Display Display | ![]() |
Images | ![]() | 56 KB | ||
Filedesc metadata | ![]() | 5.3 KB | ||
Others | ![]() ![]() | 115.9 MB 115.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 818.7 KB | Display | ![]() |
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Full document | ![]() | 818.3 KB | Display | |
Data in XML | ![]() | 13.9 KB | Display | |
Data in CIF | ![]() | 16.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8hxbMC ![]() 8hxaC ![]() 8hxcC 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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Voxel size | X=Y=Z: 0.95 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_35075_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35075_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : M2-hB7.2
Entire | Name: M2-hB7.2 |
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Components |
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-Supramolecule #1: M2-hB7.2
Supramolecule | Name: M2-hB7.2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: NFkB inhibitor
Macromolecule | Name: NFkB inhibitor / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.285348 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: VEYKNTICPP RQDYRYWYFV AELTIGVNYD INSTIIGECH MSESYIDRNA NIVLTGYGLK INMTIMDTDQ RFVAAAEGVG KDNKLSVLL FTTQRLDKVH HNISVTITCM EMNCGTTKYN SDLPESIHKS SSCDITINGS CVTCVNLETD PTKINPHYLH P KNKYLYHN ...String: VEYKNTICPP RQDYRYWYFV AELTIGVNYD INSTIIGECH MSESYIDRNA NIVLTGYGLK INMTIMDTDQ RFVAAAEGVG KDNKLSVLL FTTQRLDKVH HNISVTITCM EMNCGTTKYN SDLPESIHKS SSCDITINGS CVTCVNLETD PTKINPHYLH P KNKYLYHN SEYSMRGSYG VTFIDELNQC LLDIKELSYD ICYRE UniProtKB: Early protein OPG038 |
-Macromolecule #2: T-lymphocyte activation antigen CD86
Macromolecule | Name: T-lymphocyte activation antigen CD86 / type: protein_or_peptide / ID: 2 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.420646 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: LKIQAYFNET ADLPCQFANS QNQSLSELVV FWQDQENLVL NEVYLGKEKF DSVHSKYMGR TSFDSDSWTL RLHNLQIKDK GLYQCIIHH KKPTGMIRIH QMNSELSVLA NFSQPEIVPI SNITENVYIN LTCSSIHGYP EPKKMSVLLR TKNSTIEYDG V MQKSQDNV ...String: LKIQAYFNET ADLPCQFANS QNQSLSELVV FWQDQENLVL NEVYLGKEKF DSVHSKYMGR TSFDSDSWTL RLHNLQIKDK GLYQCIIHH KKPTGMIRIH QMNSELSVLA NFSQPEIVPI SNITENVYIN LTCSSIHGYP EPKKMSVLLR TKNSTIEYDG V MQKSQDNV TELYDVSISL SVSFPDVTSN MTIFCILETD KTRLLSSPFS IELED UniProtKB: T-lymphocyte activation antigen CD86 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | JEOL CRYO ARM 300 |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 198500 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |