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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00533024" target="_blank" >RIV/61388971:_____/20:00533024 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/20:10413060

Výsledek na webu

<a href="https://www.jbc.org/content/early/2020/05/11/jbc.RA120.013630.short" target="_blank" >https://www.jbc.org/content/early/2020/05/11/jbc.RA120.013630.short</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.RA120.013630" target="_blank" >10.1074/jbc.RA120.013630</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

—

Svazek periodika

295

Číslo periodika v rámci svazku

28

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

9349-9365

Kód UT WoS článku

000552758600008

EID výsledku v databázi Scopus

2-s2.0-85088204783