Počet záznamů: 1  

Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme?translocating segment ofBordetellaadenylate cyclase toxin

  1. 1.
    SYSNO ASEP0533024
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JČlánek ve WOS
    NázevRetargeting 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, ORCID
    Zdroj.dok.Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
    Roč. 295, č. 28 (2020), s. 9349-9365
    Poč.str.17 s.
    Jazyk dok.eng - angličtina
    Země vyd.US - Spojené státy americké
    Klíč. slovaAC domain translocation ; acylation ; acyltransferase ; fatty acyl ; integrin ; RTX toxin
    Vědní obor RIVEE - Mikrobiologie, virologie
    Obor OECDMicrobiology
    CEPGA19-04607S 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 publikováníOpen access s časovým embargem (01.08.2021)
    Institucionální podporaMBU-M - RVO:61388971
    UT WOS000552758600008
    EID SCOPUS85088204783
    DOI10.1074/jbc.RA120.013630
    AnotaceTheBordetellaadenylate 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.
    PracovištěMikrobiologický ústav
    KontaktEliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
    Rok sběru2021
    Elektronická adresahttps://www.jbc.org/content/early/2020/05/11/jbc.RA120.013630.short
Počet záznamů: 1  

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