Different roles of conserved tyrosine residues of the acylated domains in folding and activity of RTX toxins
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F21%3A00547497" target="_blank" >RIV/61388971:_____/21:00547497 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/21:10438085 RIV/00216224:14740/21:00124531
Result on the web
<a href="https://www.nature.com/articles/s41598-021-99112-3" target="_blank" >https://www.nature.com/articles/s41598-021-99112-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-021-99112-3" target="_blank" >10.1038/s41598-021-99112-3</a>
Alternative languages
Result language
angličtina
Original language name
Different roles of conserved tyrosine residues of the acylated domains in folding and activity of RTX toxins
Original language description
Pore-forming repeats in toxins (RTX) are key virulence factors of many Gram-negative pathogens. We have recently shown that the aromatic side chain of the conserved tyrosine residue 940 within the acylated segment of the RTX adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) plays a key role in target cell membrane interaction of the toxin. Therefore, we used a truncated CyaA-derived RTX719 construct to analyze the impact of Y940 substitutions on functional folding of the acylated segment of CyaA. Size exclusion chromatography combined with CD spectroscopy revealed that replacement of the aromatic side chain of Y940 by the side chains of alanine or proline residues disrupted the calcium-dependent folding of RTX719 and led to self-aggregation of the otherwise soluble and monomeric protein. Intriguingly, corresponding alanine substitutions of the conserved Y642, Y643 and Y639 residues in the homologous RtxA, HlyA and ApxIA hemolysins from Kingella kingae, Escherichia coli and Actinobacillus pleuropneumoniae, affected the membrane insertion, pore-forming (hemolytic) and cytotoxic capacities of these toxins only marginally. Activities of these toxins were impaired only upon replacement of the conserved tyrosines by proline residues. It appears, hence, that the critical role of the aromatic side chain of the Y940 residue is highly specific for the functional folding of the acylated domain of CyaA and determines its capacity to penetrate target cell membrane.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Scientific Reports
ISSN
2045-2322
e-ISSN
2045-2322
Volume of the periodical
11
Issue of the periodical within the volume
1
Country of publishing house
DE - GERMANY
Number of pages
16
Pages from-to
19814
UT code for WoS article
000706380800096
EID of the result in the Scopus database
2-s2.0-85116409448