Počet záznamů: 1
Different roles of conserved tyrosine residues of the acylated domains in folding and activity of RTX toxins
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SYSNO ASEP 0547497 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Different roles of conserved tyrosine residues of the acylated domains in folding and activity of RTX toxins Tvůrce(i) Lepesheva, Anna (MBU-M)
Osičková, Adriana (MBU-M) RID, ORCID
Holubová, Jana (MBU-M) RID, ORCID
Jurnečka, David (MBU-M) ORCID
Knoblochová, Šárka (MBU-M)
Espinosa-Vinals, Carlos Angel (MBU-M)
Bumba, Ladislav (MBU-M) RID, ORCID
Škopová, Karolína (MBU-M)
Fišer, Radovan (MBU-M) RID, ORCID
Osička, Radim (MBU-M) RID, ORCID
Šebo, Peter (MBU-M) RID, ORCID
Mašín, Jiří (MBU-M) RID, ORCIDČíslo článku 19814 Zdroj.dok. Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 11, č. 1 (2021)Poč.str. 16 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova adenylate-cyclase toxin ; escherichia-coli hemolysin ; bordetella-pertussis cyaa ; cell-invasive activity ; alpha-hemolysin ; membrane translocation ; complement receptor-3 ; fatty-acylation ; calcium ; binding Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP LM2018133 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy GA19-12695S GA ČR - Grantová agentura ČR GX19-27630X GA ČR - Grantová agentura ČR GA19-04607S GA ČR - Grantová agentura ČR Výzkumná infrastruktura CIISB II - 90127 - Masarykova univerzita Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 UT WOS 000706380800096 EID SCOPUS 85116409448 DOI 10.1038/s41598-021-99112-3 Anotace 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. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2022 Elektronická adresa https://www.nature.com/articles/s41598-021-99112-3
Počet záznamů: 1