+Open data
-Basic information
Entry | Database: PDB / ID: 8esb | ||||||
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Title | CryoEM structure of HLA-A2 bound to MAGEA8 (232-241) peptide | ||||||
Components | Beta-2-microglobulin,HLA class I antigen,MAGE-A8 peptide chimera | ||||||
Keywords | IMMUNE SYSTEM / HLA / MHC | ||||||
Function / homology | Function and homology information antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / lumenal side of endoplasmic reticulum membrane / ER to Golgi transport vesicle membrane / positive regulation of T cell mediated cytotoxicity / recycling endosome membrane / phagocytic vesicle membrane / peptide antigen binding / early endosome membrane / immune response ...antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / lumenal side of endoplasmic reticulum membrane / ER to Golgi transport vesicle membrane / positive regulation of T cell mediated cytotoxicity / recycling endosome membrane / phagocytic vesicle membrane / peptide antigen binding / early endosome membrane / immune response / external side of plasma membrane / signaling receptor binding / extracellular space / metal ion binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.12 Å | ||||||
Authors | Saotome, K. / Franklin, M.C. | ||||||
Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM. Authors: Kei Saotome / Drew Dudgeon / Kiersten Colotti / Michael J Moore / Jennifer Jones / Yi Zhou / Ashique Rafique / George D Yancopoulos / Andrew J Murphy / John C Lin / William C Olson / Matthew C Franklin / Abstract: The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity ...The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length α/β TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230-239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230-239) peptide and the closely related MAGEA8 (232-241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8esb.cif.gz | 100.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8esb.ent.gz | 64.5 KB | Display | PDB format |
PDBx/mmJSON format | 8esb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8esb_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8esb_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8esb_validation.xml.gz | 26.3 KB | Display | |
Data in CIF | 8esb_validation.cif.gz | 35.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/es/8esb ftp://data.pdbj.org/pub/pdb/validation_reports/es/8esb | HTTPS FTP |
-Related structure data
Related structure data | 28574MC 8es7C 8es8C 8es9C 8esaC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 50306.184 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-A, HLA / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: Q53Z42 |
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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 |
-Sample preparation
Component | Name: Single chain disulfide stabilized trimer of HLA-A2, Beta-2-microglobulin, MAGE-A8 peptide in complex with anti-Beta-2-microglobulin Fab 2M2 Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Cricetulus griseus (Chinese hamster) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.12 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 121731 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 93.78 Å2 | ||||||||||||||||||||||||
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