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- EMDB-20799: Integrin alpha-v beta-8 in complex with latent TGF-beta, Conforma... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-20799 | ||||||||||||||||||||||||
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Title | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iii (Primary map: sharpened. Additional map: unsharpened.) | ||||||||||||||||||||||||
![]() | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iii, sharpened map | ||||||||||||||||||||||||
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Biological species | ![]() ![]() ![]() | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.57 Å | ||||||||||||||||||||||||
![]() | Campbell MG / Cormier A / Cheng Y / Nishimura SL | ||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 1.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.6 KB 14.6 KB | Display Display | ![]() |
Images | ![]() | 87.4 KB | ||
Others | ![]() ![]() | 52 MB 52 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 78 KB | Display | ![]() |
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Full document | ![]() | 77.2 KB | Display | |
Data in XML | ![]() | 494 B | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6ujaC ![]() 6ujbC ![]() 6ujcC C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 1.2 TB Data #1: Unaligned 80-frame movies of αVβ8 integrin bound to latent TGF-β on a holey carbon grid [micrographs - multiframe] Data #2: Dose-weighted aligned micrographs of αVβ8 integrin bound to latent TGF-β on a holey carbon grid [micrographs - single frame] Data #3: Dose-weighted aligned particle stacks of αVβ8 integrin bound to latent TGF-β on a holey carbon grid [picked particles - single frame - processed]) ![]() Data size: 2.2 TB Data #1: Unaligned 80-frame movies of αVβ8 integrin bound to latent TGF-β on a graphene oxide grid [micrographs - multiframe] Data #2: Dose-weighted aligned micrographs of αVβ8 integrin bound to latent TGF-β on a graphene oxide grid [micrographs - single frame] Data #3: Dose-weighted aligned particle stacks of αVβ8 integrin bound to latent TGF-β on a graphene oxide grid [picked particles - single frame - processed]) |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iii, sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 latent TGF-beta,...
File | emd_20799_additional.map | ||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iii (Additional unsharpened map.) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Integrin alpha-v beta-8 in complex with latent TGF-beta,...
File | emd_20799_additional_1.map | ||||||||||||
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Annotation | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iii (Additional unsharpened map.) | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Binary complex of Integrin alpha-v beta-8 with Latent TGF-beta-1 ...
Entire | Name: Binary complex of Integrin alpha-v beta-8 with Latent TGF-beta-1 (L-TGF-b1) |
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Components |
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-Supramolecule #1: Binary complex of Integrin alpha-v beta-8 with Latent TGF-beta-1 ...
Supramolecule | Name: Binary complex of Integrin alpha-v beta-8 with Latent TGF-beta-1 (L-TGF-b1) type: complex / ID: 1 / Parent: 0 |
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Molecular weight | Theoretical: 260 KDa |
-Supramolecule #2: alpha-v beta-8 integrin
Supramolecule | Name: alpha-v beta-8 integrin / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Supramolecule #3: Transforming Growth Factor Beta-1 proprotein
Supramolecule | Name: Transforming Growth Factor Beta-1 proprotein / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-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: 7.5 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.57 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 31978 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |