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- PDB-7usl: Integrin alphaM/beta2 ectodomain in complex with adenylate cyclas... -

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Basic information

Entry
Database: PDB / ID: 7usl
TitleIntegrin alphaM/beta2 ectodomain in complex with adenylate cyclase toxin RTX751 and M1F5 Fab
Components
  • Bifunctional hemolysin-adenylate cyclase
  • Integrin alpha-M
  • Integrin beta
  • M1F5 fab heavy chain
  • M1F5 fab light chain
KeywordsTOXIN / Receptor / Complex / Integrin
Function / homology
Function and homology information


cellular extravasation / ectodermal cell differentiation / 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 ...cellular extravasation / ectodermal cell differentiation / 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 / cytolysis / complement-mediated synapse pruning / Toll Like Receptor 4 (TLR4) Cascade / negative regulation of dopamine metabolic process / leukocyte migration involved in inflammatory response / cell-cell adhesion via plasma-membrane adhesion molecules / complement receptor mediated signaling pathway / heterotypic cell-cell adhesion / integrin complex / cargo receptor activity / cell adhesion mediated by integrin / leukocyte cell-cell adhesion / phagocytosis, engulfment / amyloid-beta clearance / plasma membrane raft / 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 / heat shock protein binding / cell-matrix adhesion / receptor-mediated endocytosis / 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 / toxin activity / Interleukin-4 and Interleukin-13 signaling / cell adhesion / membrane raft / external side of plasma membrane / innate immune response / focal adhesion / calcium ion binding / Neutrophil degranulation / cell surface / extracellular space / extracellular exosome / extracellular region / metal ion binding / plasma membrane
Similarity search - Function
RTX, pore-forming domain / N-terminal domain in RTX protein / RTX toxin determinant A / Integrin beta-2 subunit / : / Integrin alpha-X-like, Ig-like domain 3 / Hemolysin-type calcium-binding conserved site / Hemolysin-type calcium-binding region signature. / RTX calcium-binding nonapeptide repeat / RTX calcium-binding nonapeptide repeat (4 copies) ...RTX, pore-forming domain / N-terminal domain in RTX protein / RTX toxin determinant A / Integrin beta-2 subunit / : / Integrin alpha-X-like, Ig-like domain 3 / Hemolysin-type calcium-binding conserved site / Hemolysin-type calcium-binding region signature. / RTX calcium-binding nonapeptide repeat / RTX calcium-binding nonapeptide repeat (4 copies) / Serralysin-like metalloprotease, C-terminal / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / Integrin beta tail domain / Integrin beta subunit, tail / Integrin beta tail domain superfamily / Integrin_B_tail / Integrin beta subunit, VWA domain / Integrin beta subunit / Integrin beta N-terminal / Integrin beta chain VWA domain / Integrin plexin domain / Integrins beta chain cysteine-rich domain signature. / Integrin beta subunits (N-terminal portion of extracellular region) / Integrin alpha cytoplasmic region / Integrin alpha-2 / Integrin alpha Ig-like domain 1 / : / Integrin alpha Ig-like domain 2 / Integrin alpha chain / Integrin alpha beta-propellor / Integrin alpha chain, C-terminal cytoplasmic region, conserved site / Integrins alpha chain signature. / FG-GAP repeat profile. / Integrin alpha (beta-propellor repeats). / FG-GAP repeat / FG-GAP repeat / Integrin alpha, N-terminal / Integrin domain superfamily / von Willebrand factor type A domain / PSI domain / domain found in Plexins, Semaphorins and Integrins / von Willebrand factor (vWF) type A domain / VWFA domain profile. / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / Prokaryotic membrane lipoprotein lipid attachment site profile.
Similarity search - Domain/homology
Integrin beta / Bifunctional hemolysin-adenylate cyclase / Integrin alpha-M
Similarity search - Component
Biological speciesHomo sapiens (human)
Bordetella pertussis (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å
AuthorsGoldsmith, J.A. / McLellan, J.S.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI155453 United States
CitationJournal: 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
DepositionApr 25, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 17, 2022Provider: repository / Type: Initial release
Revision 1.1Sep 14, 2022Group: Database references / Category: citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Integrin alpha-M
B: Integrin beta
C: Bifunctional hemolysin-adenylate cyclase
H: M1F5 fab heavy chain
L: M1F5 fab light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)362,30451
Polymers357,5535
Non-polymers4,75146
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: immunoprecipitation
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 3 types, 3 molecules ABC

#1: Protein Integrin alpha-M / CD11 antigen-like family member B / CR-3 alpha chain / Cell surface glycoprotein MAC-1 subunit ...CD11 antigen-like family member B / CR-3 alpha chain / Cell surface glycoprotein MAC-1 subunit alpha / Leukocyte adhesion receptor MO1 / Neutrophil adherence receptor


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
#2: Protein Integrin beta


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: Protein Bifunctional hemolysin-adenylate cyclase


Mass: 100286.688 Da / Num. of mol.: 1 / Fragment: C-terminal fragment RTX751, residues 270-1225