+Open data
-Basic information
Entry | Database: PDB / ID: 7usm | ||||||
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Title | Integrin alphaM/beta2 ectodomain | ||||||
Components |
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Keywords | CELL ADHESION / Integrin / Complement / Receptor | ||||||
Function / homology | Function and homology information ectodermal cell differentiation / cellular extravasation / positive regulation of prostaglandin-E synthase activity / response to curcumin / positive regulation of neutrophil degranulation / integrin alphaM-beta2 complex / response to Gram-positive bacterium / positive regulation of microglial cell mediated cytotoxicity / complement component C3b binding / vertebrate eye-specific patterning ...ectodermal cell differentiation / cellular extravasation / positive regulation of prostaglandin-E synthase activity / response to curcumin / positive regulation of neutrophil degranulation / integrin alphaM-beta2 complex / response to Gram-positive bacterium / positive regulation of microglial cell mediated cytotoxicity / complement component C3b binding / vertebrate eye-specific patterning / complement-mediated synapse pruning / Toll Like Receptor 4 (TLR4) Cascade / negative regulation of dopamine metabolic process / cell-cell adhesion via plasma-membrane adhesion molecules / leukocyte migration involved in inflammatory response / complement receptor mediated signaling pathway / integrin complex / heterotypic cell-cell adhesion / cargo receptor activity / cell adhesion mediated by integrin / leukocyte cell-cell adhesion / phagocytosis, engulfment / plasma membrane raft / amyloid-beta clearance / tertiary granule membrane / endothelial cell migration / positive regulation of protein targeting to membrane / Integrin cell surface interactions / specific granule membrane / phagocytosis / response to mechanical stimulus / forebrain development / cell adhesion molecule binding / heat shock protein binding / receptor-mediated endocytosis / cell-matrix adhesion / positive regulation of superoxide anion generation / response to ischemia / integrin-mediated signaling pathway / Cell surface interactions at the vascular wall / microglial cell activation / cell-cell adhesion / positive regulation of angiogenesis / positive regulation of nitric oxide biosynthetic process / integrin binding / response to estradiol / amyloid-beta binding / Interleukin-4 and Interleukin-13 signaling / cell adhesion / membrane raft / external side of plasma membrane / innate immune response / Neutrophil degranulation / protein-containing complex binding / cell surface / extracellular space / extracellular exosome / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||
Authors | Goldsmith, J.A. / McLellan, J.S. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Rep / Year: 2022 Title: Structural basis for non-canonical integrin engagement by Bordetella adenylate cyclase toxin. Authors: Jory A Goldsmith / Andrea M DiVenere / Jennifer A Maynard / Jason S McLellan / Abstract: Integrins are ubiquitous cell-surface heterodimers that are exploited by pathogens and toxins, including leukotoxins that target β integrins on phagocytes. The Bordetella adenylate cyclase toxin ...Integrins are ubiquitous cell-surface heterodimers that are exploited by pathogens and toxins, including leukotoxins that target β integrins on phagocytes. The Bordetella adenylate cyclase toxin (ACT) uses the αβ integrin as a receptor, but the structural basis for integrin binding and neutralization by antibodies is poorly understood. Here, we use cryoelectron microscopy to determine a 2.7 Å resolution structure of an ACT fragment bound to αβ. This structure reveals that ACT interacts with the headpiece and calf-2 of the α subunit in a non-canonical manner specific to bent, inactive αβ. Neutralizing antibody epitopes map to ACT residues involved in α binding, providing the basis for antibody-mediated attachment inhibition. Furthermore, binding to αβ positions the essential ACT acylation sites, which are conserved among toxins exported by type I secretion systems, at the cell membrane. These findings reveal a structural mechanism for integrin-mediated attachment and explain antibody-mediated neutralization of ACT intoxication. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7usm.cif.gz | 292.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7usm.ent.gz | 221.1 KB | Display | PDB format |
PDBx/mmJSON format | 7usm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7usm_validation.pdf.gz | 846.6 KB | Display | wwPDB validaton report |
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Full document | 7usm_full_validation.pdf.gz | 858.2 KB | Display | |
Data in XML | 7usm_validation.xml.gz | 46.1 KB | Display | |
Data in CIF | 7usm_validation.cif.gz | 68.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/us/7usm ftp://data.pdbj.org/pub/pdb/validation_reports/us/7usm | HTTPS FTP |
-Related structure data
Related structure data | 26739MC 7uslC 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: 128455.289 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ITGAM, CD11B, CR3A / Production host: Homo sapiens (human) / References: UniProt: P11215 | ||||||
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#2: Protein | Mass: 80784.938 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ITGB2 / Production host: Homo sapiens (human) / References: UniProt: A0A494C0X7 | ||||||
#3: 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 | ||||||
#4: Chemical | ChemComp-CA / #5: Sugar | ChemComp-NAG / Has ligand of interest | N | Has protein modification | Y | |
-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: Integrin alphaM/beta2 ectodomain / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
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: 2200 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 80 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1114678 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 56.42 Å2 | ||||||||||||||||||||||||
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