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Yorodumi- EMDB-20795: Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Pr... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20795 | ||||||||||||||||||||||||
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Title | Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Primary map: sharpened, focused refinement. Five additional maps.) | ||||||||||||||||||||||||
Map data | Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Primary map: sharpened, focused refinement, 3.5 A resolution. Five additional maps.) | ||||||||||||||||||||||||
Sample |
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Function / homology | Function and homology information ganglioside metabolic process / Langerhans cell differentiation / integrin alphav-beta6 complex / integrin alphav-beta8 complex / hard palate development / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / opsonin binding / integrin alphav-beta1 complex ...ganglioside metabolic process / Langerhans cell differentiation / integrin alphav-beta6 complex / integrin alphav-beta8 complex / hard palate development / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / opsonin binding / integrin alphav-beta1 complex / Cross-presentation of particulate exogenous antigens (phagosomes) / extracellular matrix protein binding / Laminin interactions / placenta blood vessel development / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / alphav-beta3 integrin-PKCalpha complex / entry into host cell by a symbiont-containing vacuole / alphav-beta3 integrin-HMGB1 complex / negative regulation of lipid transport / negative regulation of low-density lipoprotein receptor activity / regulation of phagocytosis / Elastic fibre formation / alphav-beta3 integrin-IGF-1-IGF1R complex / transforming growth factor beta binding / filopodium membrane / extracellular matrix binding / positive regulation of small GTPase mediated signal transduction / apolipoprotein A-I-mediated signaling pathway / cartilage development / apoptotic cell clearance / negative regulation of macrophage derived foam cell differentiation / wound healing, spreading of epidermal cells / heterotypic cell-cell adhesion / negative regulation of lipid storage / integrin complex / Molecules associated with elastic fibres / positive regulation of intracellular signal transduction / cell adhesion mediated by integrin / microvillus membrane / negative chemotaxis / Syndecan interactions / cell-substrate adhesion / endodermal cell differentiation / positive regulation of osteoblast proliferation / TGF-beta receptor signaling activates SMADs / PECAM1 interactions / lamellipodium membrane / fibronectin binding / positive regulation of cell adhesion / ECM proteoglycans / voltage-gated calcium channel activity / vasculogenesis / Integrin cell surface interactions / coreceptor activity / specific granule membrane / extrinsic apoptotic signaling pathway in absence of ligand / Signal transduction by L1 / phagocytic vesicle / ERK1 and ERK2 cascade / substrate adhesion-dependent cell spreading / transforming growth factor beta receptor signaling pathway / cell-matrix adhesion / integrin-mediated signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / protein kinase C binding / calcium ion transmembrane transport / cell-cell adhesion / ruffle membrane / response to virus / VEGFA-VEGFR2 Pathway / integrin binding / positive regulation of angiogenesis / virus receptor activity / cell migration / positive regulation of cytosolic calcium ion concentration / protease binding / angiogenesis / cell adhesion / positive regulation of cell migration / symbiont entry into host cell / immune response / external side of plasma membrane / negative regulation of gene expression / focal adhesion / positive regulation of cell population proliferation / Neutrophil degranulation / positive regulation of gene expression / cell surface / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol Similarity search - Function | ||||||||||||||||||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.51 Å | ||||||||||||||||||||||||
Authors | Campbell MG / Cormier A / Cheng Y / Nishimura SL | ||||||||||||||||||||||||
Funding support | United States, 7 items
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Citation | Journal: Cell / Year: 2020 Title: Cryo-EM Reveals Integrin-Mediated TGF-β Activation without Release from Latent TGF-β. Authors: Melody G Campbell / Anthony Cormier / Saburo Ito / Robert I Seed / Andrew J Bondesson / Jianlong Lou / James D Marks / Jody L Baron / Yifan Cheng / Stephen L Nishimura / Abstract: Integrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. ...Integrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. Inhibiting αvβ8-mediated TGF-β activation blocks immunosuppressive regulatory T cell differentiation, which is a potential therapeutic strategy in cancer. Using cryo-electron microscopy, structure-guided mutagenesis, and cell-based assays, we reveal the binding interactions between the entire αvβ8 ectodomain and its intact natural ligand, L-TGF-β, as well as two different inhibitory antibody fragments to understand the structural underpinnings of αvβ8 binding specificity and TGF-β activation. Our studies reveal a mechanism of TGF-β activation where mature TGF-β signals within the confines of L-TGF-β and the release and diffusion of TGF-β are not required. The structural details of this mechanism provide a rational basis for therapeutic strategies to inhibit αvβ8-mediated L-TGF-β activation. | ||||||||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20795.map.gz | 1.3 MB | EMDB map data format | |
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Header (meta data) | emd-20795-v30.xml emd-20795.xml | 31.5 KB 31.5 KB | Display Display | EMDB header |
Images | emd_20795.png | 92.5 KB | ||
Others | emd_20795_additional_1.map.gz emd_20795_additional_2.map.gz emd_20795_additional_3.map.gz emd_20795_additional_4.map.gz emd_20795_additional_5.map.gz | 2.1 MB 52.1 MB 52 MB 656.9 KB 52.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20795 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20795 | HTTPS FTP |
-Validation report
Summary document | emd_20795_validation.pdf.gz | 301.3 KB | Display | EMDB validaton report |
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Full document | emd_20795_full_validation.pdf.gz | 300.9 KB | Display | |
Data in XML | emd_20795_validation.xml.gz | 6.5 KB | Display | |
Data in CIF | emd_20795_validation.cif.gz | 7.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20795 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20795 | HTTPS FTP |
-Related structure data
Related structure data | 6ujbMC 6ujaC 6ujcC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | |
EM raw data | EMPIAR-10345 (Title: CryoEM dataset containing multiple conformations of the asymmetric αVβ8 integrin bound to two Fabs on a holey carbon grid (minimal preferred orientations) Data size: 882.1 Data #1: Unaligned 60-frame movies of αVβ8 integrin bound to a Fab (C6D4) on a holey carbon grid [micrographs - multiframe] Data #2: Dose-weighted aligned micrographs of αVβ8 integrin bound to a Fab (C6D4) on a holey carbon grid [micrographs - single frame] Data #3: Dose-weighted aligned particle stacks of αVβ8 integrin bound to a Fab (C6D4) on a holey carbon grid [picked particles - single frame - processed]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20795.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Primary map: sharpened, focused refinement, 3.5 A resolution. Five additional maps.) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.345 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Integrin alpha-v beta-8 in complex with Fabs C6D4...
File | emd_20795_additional_1.map | ||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Additional map: unsharpened, focused refinement.) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Integrin alpha-v beta-8 in complex with Fabs C6D4...
File | emd_20795_additional_2.map | ||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Additional map: sharpened, full complex, 3.8 A resolution) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Integrin alpha-v beta-8 in complex with Fabs C6D4...
File | emd_20795_additional_3.map | ||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Additional map: unsharpened, full complex.) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Integrin alpha-v beta-8 in complex with Fabs C6D4...
File | emd_20795_additional_4.map | ||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Additional map: sharpened, focused refinement ii, 3.3 A resolution) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Integrin alpha-v beta-8 in complex with Fabs C6D4...
File | emd_20795_additional_5.map | ||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with Fabs C6D4 and 11D12v2 (Additional map: unsharpened, focused refinement ii.) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Ternary complex of Integrin alpha-v beta-8 with Fab C6D4 and Fab ...
+Supramolecule #1: Ternary complex of Integrin alpha-v beta-8 with Fab C6D4 and Fab ...
+Supramolecule #2: alpha-v beta-8 integrin
+Supramolecule #3: C6D4 Fab
+Supramolecule #4: 11D12v2 Fab
+Macromolecule #1: Integrin alpha-V
+Macromolecule #2: Integrin beta-8
+Macromolecule #3: C6D4 heavy chain Fab
+Macromolecule #4: C6D4 light chain Fab
+Macromolecule #7: CALCIUM ION
+Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #9: MAGNESIUM ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.51 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 84266 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |