Počet záznamů: 1
Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme?translocating segment ofBordetellaadenylate cyclase toxin
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SYSNO ASEP 0533024 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme?translocating segment ofBordetellaadenylate cyclase toxin Tvůrce(i) Mašín, Jiří (MBU-M) RID, ORCID
Osičková, Adriana (MBU-M) RID, ORCID
Jurnečka, David (MBU-M) ORCID
Klímová, Nela (MBU-M) ORCID
Khaliq, Humaira (MBU-M)
Šebo, Peter (MBU-M) RID, ORCID
Osička, Radim (MBU-M) RID, ORCIDZdroj.dok. Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 295, č. 28 (2020), s. 9349-9365Poč.str. 17 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova AC domain translocation ; acylation ; acyltransferase ; fatty acyl ; integrin ; RTX toxin Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology CEP GA19-04607S GA ČR - Grantová agentura ČR GA18-18079S GA ČR - Grantová agentura ČR GA19-12695S GA ČR - Grantová agentura ČR GA18-20621S GA ČR - Grantová agentura ČR LM2018133 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access s časovým embargem (01.08.2021) Institucionální podpora MBU-M - RVO:61388971 UT WOS 000552758600008 EID SCOPUS 85088204783 DOI 10.1074/jbc.RA120.013630 Anotace TheBordetellaadenylate cyclase toxin-hemolysin (CyaA) and the ?-hemolysin (HlyA) ofEscherichia colibelong to the family of cytolytic pore-forming Repeats in ToXin (RTX) cytotoxins. HlyA preferentially binds the ?(L)?(2)integrin LFA-1 (CD11a/CD18) of leukocytes and can promiscuously bind and also permeabilize many other cells. CyaA bears an N-terminal adenylyl cyclase (AC) domain linked to a pore-forming RTX cytolysin (Hly) moiety, binds the complement receptor 3 (CR3, ?(M)?(2), CD11b/CD18, or Mac-1) of myeloid phagocytes, penetrates their plasma membrane, and delivers the AC enzyme into the cytosol. We constructed a set of CyaA/HlyA chimeras and show that the CyaC-acylated segment and the CR3-binding RTX domain of CyaA can be functionally replaced by the HlyC-acylated segment and the much shorter RTX domain of HlyA. Instead of binding CR3, a CyaA(1-710)/HlyA(411-1024)chimera bound the LFA-1 receptor and effectively delivered AC into Jurkat T cells. At high chimera concentrations (25 nm), the interaction with LFA-1 was not required for CyaA(1-710)/HlyA(411-1024)binding to CHO cells. However, interaction with the LFA-1 receptor strongly enhanced the specific capacity of the bound CyaA(1-710)/HlyA(411-1024)chimera to penetrate cells and deliver the AC enzyme into their cytosol. Hence, interaction of the acylated segment and/or the RTX domain of HlyA with LFA-1 promoted a productive membrane interaction of the chimera. These results help delimit residues 400?710 of CyaA as an ?AC translocon? sufficient for translocation of the AC polypeptide across the plasma membrane of target cells. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2021 Elektronická adresa https://www.jbc.org/content/early/2020/05/11/jbc.RA120.013630.short
Počet záznamů: 1