Crystal structures of the components of the Staphylococcus aureus leukotoxin ED
Abstract
Staphylococcal leukotoxins are a family of β-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins thatStaphylococcus aureusproduces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays inS. aureuspathogenesis and the identification of its protein receptors, combined with its presence inS. aureusmethicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE and LukD components of LukED have been determined. Lastly, the two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex.
- Authors:
-
- Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine, Center for Structural Genomics of Infectious Diseases, Dept. of Biochemistry and Molecular Genetics
- Novartis Vaccines and Diagnostics, Research Centre, Siena (Italy)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH)
- OSTI Identifier:
- 1233746
- Grant/Contract Number:
- AC02-06CH11357; HHSN272200700058C; HHSN272201200026C
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Acta Crystallographica. Section D. Structural Biology
- Additional Journal Information:
- Journal Volume: 72; Journal Issue: 1; Journal ID: ISSN 2059-7983
- Publisher:
- IUCr
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; LukE; LukD; leukotoxin; poreforming toxins; Staphylococcus aureus
Citation Formats
Nocadello, S., Minasov, G., Shuvalova, L., Dubrovska, I., Sabini, E., Bagnoli, F., Grandi, G., and Anderson, W. F. Crystal structures of the components of the Staphylococcus aureus leukotoxin ED. United States: N. p., 2016.
Web. doi:10.1107/S2059798315023207.
Nocadello, S., Minasov, G., Shuvalova, L., Dubrovska, I., Sabini, E., Bagnoli, F., Grandi, G., & Anderson, W. F. Crystal structures of the components of the Staphylococcus aureus leukotoxin ED. United States. https://doi.org/10.1107/S2059798315023207
Nocadello, S., Minasov, G., Shuvalova, L., Dubrovska, I., Sabini, E., Bagnoli, F., Grandi, G., and Anderson, W. F. Fri .
"Crystal structures of the components of the Staphylococcus aureus leukotoxin ED". United States. https://doi.org/10.1107/S2059798315023207. https://www.osti.gov/servlets/purl/1233746.
@article{osti_1233746,
title = {Crystal structures of the components of the Staphylococcus aureus leukotoxin ED},
author = {Nocadello, S. and Minasov, G. and Shuvalova, L. and Dubrovska, I. and Sabini, E. and Bagnoli, F. and Grandi, G. and Anderson, W. F.},
abstractNote = {Staphylococcal leukotoxins are a family of β-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins thatStaphylococcus aureusproduces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays inS. aureuspathogenesis and the identification of its protein receptors, combined with its presence inS. aureusmethicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE and LukD components of LukED have been determined. Lastly, the two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex.},
doi = {10.1107/S2059798315023207},
journal = {Acta Crystallographica. Section D. Structural Biology},
number = 1,
volume = 72,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 2016},
month = {Fri Jan 01 00:00:00 EST 2016}
}
Web of Science
Works referenced in this record:
Staphylococcus aureus leucocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo: LukED contributes to S. aureus bacteraemia
journal, December 2011
- Alonzo III, Francis; Benson, Meredith A.; Chen, John
- Molecular Microbiology, Vol. 83, Issue 2
CCR5 is a receptor for Staphylococcus aureus leukotoxin ED
journal, December 2012
- Alonzo III, Francis; Kozhaya, Lina; Rawlings, Stephen A.
- Nature, Vol. 493, Issue 7430
Bacterial Survival Amidst an Immune Onslaught: The Contribution of the Staphylococcus aureus Leukotoxins
journal, February 2013
- Alonzo, Francis; Torres, Victor J.
- PLoS Pathogens, Vol. 9, Issue 2
The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus
journal, May 2014
- Alonzo, Francis; Torres, Victor J.
- Microbiology and Molecular Biology Reviews, Vol. 78, Issue 2
Structure-Function Analysis of Heterodimer Formation, Oligomerization, and Receptor Binding of the Staphylococcus aureus Bi-component Toxin LukGH
journal, November 2014
- Badarau, Adriana; Rouha, Harald; Malafa, Stefan
- Journal of Biological Chemistry, Vol. 290, Issue 1
In vitro effects of staphylococcal leukocidin LukE/LukD on the proliferative ability of lymphocytes isolated from common carp (Cyprinus carpio L.)
journal, April 2006
- Bownik, Adam
- Fish & Shellfish Immunology, Vol. 20, Issue 4
Cell targeting by the Staphylococcus aureus pore-forming toxins: it's not just about lipids
journal, January 2014
- DuMont, Ashley L.; Torres, Victor J.
- Trends in Microbiology, Vol. 22, Issue 1
Prevalence of genes encoding for members of the staphylococcal leukotoxin family among clinical isolates of Staphylococcus aureus
journal, July 2004
- von Eiff, Christof; Friedrich, Alexander W.; Peters, Georg
- Diagnostic Microbiology and Infectious Disease, Vol. 49, Issue 3
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
The interaction of Staphylococcus aureus bi-component γ-hemolysins and leucocidins with cells and lipid membranes
journal, November 1998
- Ferreras, Mercedes; Höper, Frank; Dalla Serra, Mauro
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1414, Issue 1-2
α-Hemolysin, γ-hemolysin, and leukocidin from Staphylococcus aureus: Distant in sequence but similar in structure
journal, December 1997
- Gouaux, Eric; Hobaugh, Michael; Song, Langzhou
- Protein Science, Vol. 6, Issue 12
Crystal Structure of Leucotoxin S Component: NEW INSIGHT INTO THE STAPHYLOCOCCAL β-BARREL PORE-FORMING TOXINS
journal, July 2004
- Guillet, Valérie; Roblin, Pierre; Werner, Sandra
- Journal of Biological Chemistry, Vol. 279, Issue 39
The Polymerase Incomplete Primer Extension (PIPE) Method Applied to High-Throughput Cloning and Site-Directed Mutagenesis
book, January 2009
- Klock, Heath E.; Lesley, Scott A.
- Methods in Molecular Biology
Residues Essential for Panton-Valentine Leukocidin S Component Binding to Its Cell Receptor Suggest Both Plasticity and Adaptability in Its Interaction Surface
journal, March 2014
- Laventie, Benoit-Joseph; Guérin, Frédéric; Mourey, Lionel
- PLoS ONE, Vol. 9, Issue 3
Emergence of a Clinical Daptomycin-Resistant Staphylococcus aureus Isolate during Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia and Osteomyelitis
journal, February 2006
- Marty, F. M.; Yeh, W. W.; Wennersten, C. B.
- Journal of Clinical Microbiology, Vol. 44, Issue 2
Staphylococcus aureus innate immune evasion is lineage-specific: A bioinfomatics study
journal, October 2013
- McCarthy, Alex J.; Lindsay, Jodi A.
- Infection, Genetics and Evolution, Vol. 19
Likelihood-enhanced fast translation functions
journal, March 2005
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Storoni, Laurent C.
- Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 4
Ion channels and bacterial infection: the case of β-barrel pore-forming protein toxins of Staphylococcus aureus
journal, August 2003
- Menestrina, G.; Dalla Serra, M.; Comai, M.
- FEBS Letters, Vol. 552, Issue 1
REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011
- Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A.
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
Single-molecule imaging of cooperative assembly of -hemolysin on erythrocyte membranes
journal, October 2003
- Nguyen, V. T.
- The EMBO Journal, Vol. 22, Issue 19
[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997
- Otwinowski, Zbyszek; Minor, Wladek
- Macromolecular Crystallography Part A, 307-326
The structure of a Staphylococcus aureus leucocidin component (LukF-PV) reveals the fold of the water-soluble species of a family of transmembrane pore-forming toxins
journal, March 1999
- Pédelacq, Jean-Denis; Maveyraud, Laurent; Prévost, Gilles
- Structure, Vol. 7, Issue 3
The Influence of Membrane Lipids in Staphylococcus aureus Gamma-Hemolysins Pore Formation
journal, December 2008
- Potrich, C.; Bastiani, H.; Colin, D. A.
- Journal of Membrane Biology, Vol. 227, Issue 1
Staphylococcus aureus Leukotoxin ED Targets the Chemokine Receptors CXCR1 and CXCR2 to Kill Leukocytes and Promote Infection
journal, October 2013
- Reyes-Robles, Tamara; Alonzo, Francis; Kozhaya, Lina
- Cell Host & Microbe, Vol. 14, Issue 4
Deciphering key features in protein structures with the new ENDscript server
journal, April 2014
- Robert, Xavier; Gouet, Patrice
- Nucleic Acids Research, Vol. 42, Issue W1
A covalent S-F heterodimer of leucotoxin reveals molecular plasticity of β-barrel pore-forming toxins
journal, April 2008
- Roblin, Pierre; Guillet, Valérie; Joubert, Olivier
- Proteins: Structure, Function, and Bioinformatics, Vol. 71, Issue 1
Methicillin-resistant Staphylococcus aureus of lineage ST398 as cause of mastitis in cows
journal, October 2014
- Silva, N. C. C.; Guimarães, F. F.; Manzi, M. P.
- Letters in Applied Microbiology, Vol. 59, Issue 6
Structure of Staphylococcal alpha -Hemolysin, a Heptameric Transmembrane Pore
journal, December 1996
- Song, L.; Hobaugh, M. R.; Shustak, C.
- Science, Vol. 274, Issue 5294
Staphylococcus aureus Hemolysins, bi-component Leukocidins, and Cytolytic Peptides: A Redundant Arsenal of Membrane-Damaging Virulence Factors?
journal, January 2012
- Vandenesch, François; Lina, G.; Henry, Thomas
- Frontiers in Cellular and Infection Microbiology, Vol. 2
The participation of phospholipids in the interaction of leucocidin and the cell membrane of the polymorphonuclear leucocyte
journal, December 1967
- Woodin, A. M.; Wieneke, Antonnette A.
- Biochemical Journal, Vol. 105, Issue 3
Staphylococcal Leucocidin (Neisser-Wechsberg Type) and Antileucocidin
journal, May 1936
- Wright, Joyce
- The Lancet, Vol. 227, Issue 5879
Crystal structure of the octameric pore of staphylococcal -hemolysin reveals the -barrel pore formation mechanism by two components
journal, October 2011
- Yamashita, K.; Kawai, Y.; Tanaka, Y.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 42
Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins
journal, September 2014
- Yamashita, Daichi; Sugawara, Takaki; Takeshita, Miyu
- Nature Communications, Vol. 5, Issue 1
Cryo-EM structure of the respiratory syncytial virus RNA polymerase
journal, January 2020
- Cao, Dongdong; Gao, Yunrong; Roesler, Claire
- Nature Communications, Vol. 11, Issue 1
Works referencing / citing this record:
Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus
journal, January 2017
- Koop, Gerrit; Vrieling, Manouk; Storisteanu, Daniel M. L.
- Scientific Reports, Vol. 7, Issue 1
Structural and immunological characterization of E. coli derived recombinant CRM197 protein used as carrier in conjugate vaccines
journal, September 2018
- Mishra, Ravi P. N.; Yadav, Ravi S. P.; Jones, Christopher
- Bioscience Reports, Vol. 38, Issue 5
Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration
journal, December 2018
- Haapasalo, Karita; Wollman, Adam J. M.; Haas, Carla J. C.
- The FASEB Journal, Vol. 33, Issue 3
Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration
posted_content, April 2018
- Haapasalo, Karita; Wollman, Adam J. M.; de Haas, Carla
- bioRxiv
Structure-Based Discovery of a Novel Small-Molecule Inhibitor of Methicillin-Resistant S. aureus
posted_content, October 2019
- Liu, Jie; Kozhaya, Lina; Torres, Victor J.
- bioRxiv
Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus.
text, January 2017
- Koop, Gerrit; Vrieling, Manouk; Storisteanu, Daniel ML
- Apollo - University of Cambridge Repository