+Open data
-Basic information
Entry | Database: PDB / ID: 6djp | |||||||||||||||||||||
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Title | Integrin alpha-v beta-8 in complex with the Fabs 8B8 and 68 | |||||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / GLYCOPROTEIN / ADHESION / FAB | |||||||||||||||||||||
Function / homology | Function and homology information ganglioside metabolic process / Langerhans cell differentiation / integrin alphav-beta8 complex / integrin alphav-beta6 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-beta8 complex / integrin alphav-beta6 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 / negative regulation of lipoprotein metabolic process / integrin alphav-beta3 complex / negative regulation of low-density lipoprotein receptor activity / alphav-beta3 integrin-PKCalpha complex / alphav-beta3 integrin-HMGB1 complex / regulation of phagocytosis / negative regulation of lipid transport / Elastic fibre formation / alphav-beta3 integrin-IGF-1-IGF1R complex / transforming growth factor beta binding / entry into host cell by a symbiont-containing vacuole / positive regulation of small GTPase mediated signal transduction / filopodium membrane / extracellular matrix binding / apolipoprotein A-I-mediated signaling pathway / apoptotic cell clearance / wound healing, spreading of epidermal cells / cartilage development / positive regulation of intracellular signal transduction / heterotypic cell-cell adhesion / integrin complex / Molecules associated with elastic fibres / microvillus membrane / cell adhesion mediated by integrin / 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 / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / ECM proteoglycans / voltage-gated calcium channel activity / Integrin cell surface interactions / vasculogenesis / specific granule membrane / phagocytic vesicle / coreceptor activity / extrinsic apoptotic signaling pathway in absence of ligand / ERK1 and ERK2 cascade / positive regulation of cell adhesion / cell-matrix adhesion / substrate adhesion-dependent cell spreading / transforming growth factor beta receptor signaling pathway / Signal transduction by L1 / integrin-mediated signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / calcium ion transmembrane transport / protein kinase C binding / response to virus / VEGFA-VEGFR2 Pathway / cell-cell adhesion / ruffle membrane / positive regulation of angiogenesis / cell migration / integrin binding / virus receptor activity / positive regulation of cytosolic calcium ion concentration / protease binding / angiogenesis / cell adhesion / positive regulation of cell migration / immune response / symbiont entry into host cell / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.8 Å | |||||||||||||||||||||
Authors | Cormier, A. / Campbell, M.G. / Nishimura, S.L. / Cheng, Y. | |||||||||||||||||||||
Funding support | United States, 6items
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Citation | Journal: Nat Struct Mol Biol / Year: 2018 Title: Cryo-EM structure of the αvβ8 integrin reveals a mechanism for stabilizing integrin extension. Authors: Anthony Cormier / Melody G Campbell / Saburo Ito / Shenping Wu / Jianlong Lou / James Marks / Jody L Baron / Stephen L Nishimura / Yifan Cheng / Abstract: Integrins are conformationally flexible cell surface receptors that survey the extracellular environment for their cognate ligands. Interactions with ligands are thought to be linked to global ...Integrins are conformationally flexible cell surface receptors that survey the extracellular environment for their cognate ligands. Interactions with ligands are thought to be linked to global structural rearrangements involving transitions between bent, extended-closed and extended-open forms. Thus far, structural details are lacking for integrins in the extended conformations due to extensive flexibility between the headpiece and legs in this conformation. Here we present single-particle electron cryomicroscopy structures of human αvβ8 integrin in the extended-closed conformation, which has been considered to be a low-affinity intermediate. Our structures show the headpiece rotating about a flexible αv knee, suggesting a ligand surveillance mechanism for integrins in their extended-closed form. Our model predicts that the extended conformation is mainly stabilized by an interface formed between flexible loops in the upper and lower domains of the αv leg. Confirming these findings with the αvβ3 integrin suggests that our model of stabilizing the extended-closed conformation is generalizable to other integrins. | |||||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6djp.cif.gz | 255.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6djp.ent.gz | 164.8 KB | Display | PDB format |
PDBx/mmJSON format | 6djp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6djp_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 6djp_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6djp_validation.xml.gz | 36.6 KB | Display | |
Data in CIF | 6djp_validation.cif.gz | 59.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dj/6djp ftp://data.pdbj.org/pub/pdb/validation_reports/dj/6djp | HTTPS FTP |
-Related structure data
Related structure data | 7939MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 106758.266 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ITGAV, MSK8, VNRA, VTNR / Cell line (production host): CHO lec 3.2.8.1 / Organ (production host): ovary / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P06756 |
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#2: Protein | Mass: 70837.234 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ITGB8 / Cell line (production host): CHO lec 3.2.8.1 / Organ (production host): ovary / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P26012 |
-Antibody , 4 types, 4 molecules CDEF
#3: Antibody | Mass: 23314.826 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): hybridoma / Production host: Mus musculus (house mouse) |
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#4: Antibody | Mass: 23241.596 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): hybridoma / Production host: Mus musculus (house mouse) |
#5: Antibody | Mass: 22680.303 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): CHO / Organ (production host): ovary / Production host: Cricetulus griseus (Chinese hamster) |
#6: Antibody | Mass: 23420.795 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): CHO / Organ (production host): ovary / Production host: Cricetulus griseus (Chinese hamster) |
-Sugars , 4 types, 10 molecules
#7: 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 #8: Polysaccharide | alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D- ...alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #9: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #10: Sugar | |
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-Details
Has protein modification | Y |
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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: Alpha-v Beta-8 Integrin in complex with the Fabs 68 and 8B8 Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.312 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 6.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293 K |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
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Microscopy | Model: FEI POLARA 300 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 6 sec. / Electron dose: 41 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 713 |
Image scans | Movie frames/image: 30 |
-Processing
Software | Name: PHENIX / Version: 1.12_2829: / Classification: refinement | ||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 17442 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Refine LS restraints |
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