Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme?translocating segment ofBordetellaadenylate cyclase toxin
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11310/20:10413060
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme?translocating segment ofBordetellaadenylate cyclase toxin
Original language description
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.
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
10606 - Microbiology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Biological Chemistry
ISSN
0021-9258
e-ISSN
—
Volume of the periodical
295
Issue of the periodical within the volume
28
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
9349-9365
UT code for WoS article
000552758600008
EID of the result in the Scopus database
2-s2.0-85088204783