Leukocidin
{{short description|Pore-forming toxin produced by the bacteria Staphylococcus}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox nonhuman protein
| Name = Leukocidin D (F subunit)
| Organism = Staphylococcus aureus (strain NCTC 8325)
| TaxID = 1280
| Symbol = lukD
| AltSymbols = SAOUHSC_01954
| EntrezGene = 3920899
| RefSeqmRNA =
| RefSeqProtein = YP_500453
| UniProt = Q2FYW0
| PDB = 4Q7G
| Chromosome = genomic
| EntrezChromosome = NC_007795.1
| GenLoc_start = 1858862
| GenLoc_end = 1860139
}}
{{Infobox nonhuman protein
| Name = Leukocidin E (S subunit)
| Organism = Staphylococcus aureus (strain NCTC 8325)
| TaxID = 1280
| Symbol = lukE
| AltSymbols = SAOUHSC_01955
| EntrezGene = 3920899
| RefSeqmRNA =
| RefSeqProtein = YP_500453
| UniProt = Q2FYW1
| PDB = 3ROH
| Chromosome = genomic
| EntrezChromosome = NC_007795.1
| GenLoc_start = 1858862
| GenLoc_end = 1860139
}}
A leukocidin is a type of cytotoxin created by some types of bacteria (Staphylococcus). It is a type of pore-forming toxin. Leukocidins fall into the category of bacterial invasin. Invasins are enzymatic secretions that help bacteria invade the host tissue to which they are attached. Although similar to exotoxins, invasins are different in two respects: they work through much less specific mechanisms than exotoxins, and their actions are generally more localized.
Leukocidins get their names by killing ("-cide") leukocytes. Leukocidins target phagocytes, natural killer cells, dendritic cells, and T lymphocytes,{{Cite journal | vauthors = Alonzo III F, Kozhaya L, Rawlings SA, Reyes-Robles T, DuMont AL, Myszka DG, Landau NR, Unutmaz D, Torres VJ | title = CCR5 is a receptor for Staphylococcus aureus leukotoxin ED | journal = Nature | volume = 493 | issue = 7430 | pages = 51–55 | date = 2012-12-12 | pmid = 23235831 | pmc = 3536884 | doi = 10.1038/nature11724 | issn = 0028-0836 }} and therefore affect both innate and adaptive immune responses.
Mechanism of action
Leukocidins are pore-forming toxins, and their model for pore formation is step-wise.
First, the cytotoxin's "S" subunit recognizes specific protein-containing receptors, typically G-protein coupled receptors, or an integrin on the host cell's surface. The S subunit then recruits a second, "F" subunit. The two subunits dimerize on the host cell surface. This dimerization is followed by oligomerization involving three additional leukocidin dimers, resulting in an octameric prepore complex.
The prepore undergoes a structural transition in which its prestem domain extends into the lipid bilayer, forming a beta barrel that pierces the target cell membrane, thereby disrupting the structure of the cell and leading to lysis.{{Cite journal | vauthors = Alonzo F, Torres VJ | title = The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus | journal = Microbiology and Molecular Biology Reviews | volume = 78 | issue = 2 | pages = 199–230 | date = 2014-05-20 | pmid = 24847020 | pmc = 4054254 | doi = 10.1128/mmbr.00055-13 | issn = 1092-2172 }}
Subunits: S and F
The F subunit stands for the "fast" subunit while the S subunit stands for the "slow" subunit.{{Cite journal | vauthors = Schiepers A, de Haas CJ, van Hooijdonk DD, Badiou C, Contamin H, Vandenesch F, Lina G, Gerard NP, Gerard C, van Kessel KP, Henry T, van Strijp JA, Spaan AN | title = Differential Interaction of the Staphylococcal Toxins Panton–Valentine Leukocidin and γ-Hemolysin CB with Human C5a Receptors | journal = The Journal of Immunology | volume = 195 | issue = 3 | pages = 1034–1043 | date = 2015-08-01 | pmid = 26091719 | doi = 10.4049/jimmunol.1500604 | url = https://journals.aai.org/jimmunol/article/195/3/1034/104702 | issn = 0022-1767 | pmc = 4506853 }} The S subunit is the first to bind the lipid bilayer, recognizing the cell surface receptor. Once bound, the F subunit dimerizes with the S subunit to initiate pore assembly.
Variatiants
There are exceptions to the typical binding pattern of leukocidins. For example:
- LukPQ: In this case, the F subunit (rather than the S subunit) recognizes the cell surface receptor.
- LukAB: This leukocidin binds to the integrin CD11b, not a G-protein coupled receptor.{{Cite journal | vauthors = Torres VJ, Tam K | title = Staphylococcus aureus Secreted Toxins and Extracellular Enzymes | journal = Microbiology Spectrum | volume = 7 | issue = 2 | date = March 2019 | pmid = 30873936 | pmc = 6422052 | doi = 10.1128/microbiolspec.GPP3-0039-2018 | issn = 2165-0497 }}
Examples
One notable type of leukocidin is the Panton-Valentine leukocidin.
References
{{Reflist}}
External links
- {{MeshName|Leukocidins}}
{{Toxins}}
{{Membrane proteins}}
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