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Open data
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Basic information
Entry | Database: PDB / ID: 6eny | ||||||||||||
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Title | Structure of the human PLC editing module | ||||||||||||
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![]() | IMMUNE SYSTEM / adaptive immunity / antigen processing / chaperone / MHC class I | ||||||||||||
Function / homology | ![]() MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / Calnexin/calreticulin cycle / MHC class I protein complex binding / TAP1 binding / TAP2 binding / cytolytic granule / positive regulation of dendritic cell chemotaxis / protein disulfide-isomerase ...MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / Calnexin/calreticulin cycle / MHC class I protein complex binding / TAP1 binding / TAP2 binding / cytolytic granule / positive regulation of dendritic cell chemotaxis / protein disulfide-isomerase / cortical granule / Assembly of Viral Components at the Budding Site / negative regulation of trophoblast cell migration / ATF6 (ATF6-alpha) activates chaperone genes / negative regulation of retinoic acid receptor signaling pathway / cellular response to electrical stimulus / endoplasmic reticulum quality control compartment / complement component C1q complex binding / nuclear receptor-mediated glucocorticoid signaling pathway / regulation of meiotic nuclear division / response to glycoside / sequestering of calcium ion / sarcoplasmic reticulum lumen / protein folding in endoplasmic reticulum / hormone binding / disulfide oxidoreductase activity / nuclear export signal receptor activity / negative regulation of intracellular steroid hormone receptor signaling pathway / regulation of protein complex stability / cardiac muscle cell differentiation / molecular sequestering activity / phospholipase C activity / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / positive regulation of extrinsic apoptotic signaling pathway / cellular response to interleukin-7 / protein maturation by protein folding / Scavenging by Class F Receptors / Scavenging by Class A Receptors / cortical actin cytoskeleton organization / T cell mediated cytotoxicity directed against tumor cell target / positive regulation of memory T cell activation / TAP complex binding / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / nuclear androgen receptor binding / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell proliferation / cellular response to lithium ion / CD8 receptor binding / response to testosterone / protein disulfide isomerase activity / MHC class I protein binding / antigen processing and presentation of exogenous peptide antigen via MHC class I / endoplasmic reticulum exit site / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / TAP binding / protein localization to nucleus / protection from natural killer cell mediated cytotoxicity / protein-disulfide reductase activity / negative regulation of neuron differentiation / smooth endoplasmic reticulum / beta-2-microglobulin binding / T cell receptor binding / positive regulation of cell cycle / detection of bacterium / ERAD pathway / positive regulation of substrate adhesion-dependent cell spreading / extrinsic apoptotic signaling pathway / positive regulation of phagocytosis / phagocytic vesicle / protein folding chaperone / endocytic vesicle lumen / protein export from nucleus / positive regulation of endothelial cell migration / endoplasmic reticulum-Golgi intermediate compartment membrane / response to endoplasmic reticulum stress / acrosomal vesicle / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of receptor binding / early endosome lumen / peptide binding / Nef mediated downregulation of MHC class I complex cell surface expression / negative regulation of receptor binding / DAP12 interactions / 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 / cellular response to iron ion / Endosomal/Vacuolar pathway / lumenal side of endoplasmic reticulum membrane / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / cellular response to iron(III) ion / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / negative regulation of forebrain neuron differentiation / regulation of erythrocyte differentiation / peptide antigen assembly with MHC class I protein complex / ER to Golgi transport vesicle membrane / regulation of iron ion transport / response to molecule of bacterial origin / positive regulation of non-canonical NF-kappaB signal transduction Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.8 Å | ||||||||||||
![]() | Trowitzsch, S. / Januliene, D. / Blees, A. / Moeller, A. / Tampe, R. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of the human MHC-I peptide-loading complex. Authors: Andreas Blees / Dovile Januliene / Tommy Hofmann / Nicole Koller / Carla Schmidt / Simon Trowitzsch / Arne Moeller / Robert Tampé / ![]() Abstract: The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates ...The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules. After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells. Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin. The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex. Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy. Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I are centred around TAP in a pseudo-symmetric orientation. A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules. The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57. This arrangement allows tapasin to facilitate peptide editing by clamping MHC-I. The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I. Two lateral windows channel the antigenic peptides to MHC-I. Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I. Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response. | ||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 257.1 KB | Display | ![]() |
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PDB format | ![]() | 168 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 3906MC ![]() 3904C ![]() 3905C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
-Protein , 5 types, 5 molecules BCDFG
#1: Protein | Mass: 11748.160 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: Protein | Mass: 45761.184 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: Protein | Mass: 54341.102 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#4: Protein | Mass: 38363.535 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#5: Protein | Mass: 46507.145 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Sugars , 2 types, 2 molecules
#6: 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 |
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#7: Polysaccharide | beta-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose Type: oligosaccharide / Mass: 666.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source |
-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: Protein Complex / Type: COMPLEX / Entity ID: #1-#5 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: C-flat-2/2 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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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 |
Image recording | Electron dose: 55 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
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Processing
EM software |
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CTF correction | Details: CTF correction was performed internally in Relion and Frealign Type: NONE | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 5.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 141078 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Refinement | Highest resolution: 5.8 Å |