Acyltransferase-mediated selection of the length of the fatty
acyl chain and of the acylation site governs activation of
bacterial RTX toxins

J 2020

Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins

OSICKOVA, Adriana; Humaira KHALIQ; Jiri MASIN; David JURNECKA; Anna SUKOVA et. al.

Basic information

Original name

Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins

Authors

OSICKOVA, Adriana; Humaira KHALIQ; Jiri MASIN; David JURNECKA; Anna SUKOVA; Radovan FISER; Jana HOLUBOVA; Ondrej STANEK; Peter SEBO and Radim OSICKA

Edition

International Journal of Biological Chemistry, AMSTERDAM, ANSInet, 2020, 1819-155X

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Netherlands

Confidentiality degree

is not subject to a state or trade secret

References:

URL

RIV identification code

RIV/00216224:90127/20:00139236

DOI

https://doi.org/10.1074/jbc.RA120.014122

UT WoS

000552758600001

EID Scopus

2-s2.0-85088202515

Keywords in English

acylation; acyltransferase; cytotoxicity; fatty acyl; RTX toxin; posttranslational modification; adenylate cyclase toxin (CyaA); ?-hemolysin (HlyA); cytotoxin (RtxA); protoxin; protein acylation; fatty acid; bacterial toxin; protein translocation

Abstract

In the original language

In a wide range of organisms, from bacteria to humans, numerous proteins have to be posttranslationally acylated to become biologically active. Bacterialrepeats intoxin (RTX) cytolysins form a prominent group of proteins that are synthesized as inactive protoxins and undergo posttranslational acylation on ?-amino groups of two internal conserved lysine residues by co-expressed toxin-activating acyltransferases. Here, we investigated how the chemical nature, position, and number of bound acyl chains govern the activities ofBordetella pertussisadenylate cyclase toxin (CyaA),Escherichia coli?-hemolysin (HlyA), andKingella kingaecytotoxin (RtxA). We found that the three protoxins are acylated in the sameE. colicell background by each of the CyaC, HlyC, and RtxC acyltransferases. We also noted that the acyltransferase selects from the bacterial pool of acyl?acyl carrier proteins (ACPs) an acyl chain of a specific length for covalent linkage to the protoxin. The acyltransferase also selects whether both or only one of two conserved lysine residues of the protoxin will be posttranslationally acylated. Functional assays revealed that RtxA has to be modified by 14-carbon fatty acyl chains to be biologically active, that HlyA remains active also when modified by 16-carbon acyl chains, and that CyaA is activated exclusively by 16-carbon acyl chains. These results suggest that the RTX toxin molecules are structurally adapted to the length of the acyl chains used for modification of their acylated lysine residue in the second, more conserved acylation site.

Links

90127, large research infrastructures

Name: CIISB II

Cite

OSICKOVA, Adriana; Humaira KHALIQ; Jiri MASIN; David JURNECKA; Anna SUKOVA; Radovan FISER; Jana HOLUBOVA; Ondrej STANEK; Peter SEBO and Radim OSICKA. Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins. International Journal of Biological Chemistry. AMSTERDAM: ANSInet, 2020, vol. 295, No 28, p. 9268-9280. ISSN 1819-155X. Available from: https://doi.org/10.1074/jbc.RA120.014122.

@article{2487417,
   author = {Osickova, Adriana and Khaliq, Humaira and Masin, Jiri and Jurnecka, David and Sukova, Anna and Fiser, Radovan and Holubova, Jana and Stanek, Ondrej and Sebo, Peter and Osicka, Radim},
   article_location = {AMSTERDAM},
   article_number = {28},
   doi = {https://doi.org/10.1074/jbc.RA120.014122},
   keywords = {acylation; acyltransferase; cytotoxicity; fatty acyl; RTX toxin; posttranslational modification; adenylate cyclase toxin (CyaA); ?-hemolysin (HlyA); cytotoxin (RtxA); protoxin; protein acylation; fatty acid; bacterial toxin; protein translocation},
   language = {eng},
   issn = {1819-155X},
   journal = {International Journal of Biological Chemistry},
   title = {Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins},
   url = {https://www.jbc.org/article/S0021-9258(17)48951-4/fulltext},
   volume = {295},
   year = {2020}
}

TY  - JOUR
ID  - 2487417
AU  - Osickova, Adriana - Khaliq, Humaira - Masin, Jiri - Jurnecka, David - Sukova, Anna - Fiser, Radovan - Holubova, Jana - Stanek, Ondrej - Sebo, Peter - Osicka, Radim
PY  - 2020
TI  - Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins
JF  - International Journal of Biological Chemistry
VL  - 295
IS  - 28
SP  - 9268-9280
EP  - 9268-9280
PB  - ANSInet
SN  - 1819155X
KW  - acylation
KW  - acyltransferase
KW  - cytotoxicity
KW  - fatty acyl
KW  - RTX toxin
KW  - posttranslational modification
KW  - adenylate cyclase toxin (CyaA)
KW  - ?-hemolysin (HlyA)
KW  - cytotoxin (RtxA)
KW  - protoxin
KW  - protein acylation
KW  - fatty acid
KW  - bacterial toxin
KW  - protein translocation
UR  - https://www.jbc.org/article/S0021-9258(17)48951-4/fulltext
N2  - In a wide range of organisms, from bacteria to humans, numerous proteins have to be posttranslationally acylated to become biologically active. Bacterialrepeats intoxin (RTX) cytolysins form a prominent group of proteins that are synthesized as inactive protoxins and undergo posttranslational acylation on ?-amino groups of two internal conserved lysine residues by co-expressed toxin-activating acyltransferases. Here, we investigated how the chemical nature, position, and number of bound acyl chains govern the activities ofBordetella pertussisadenylate cyclase toxin (CyaA),Escherichia coli?-hemolysin (HlyA), andKingella kingaecytotoxin (RtxA). We found that the three protoxins are acylated in the sameE. colicell background by each of the CyaC, HlyC, and RtxC acyltransferases. We also noted that the acyltransferase selects from the bacterial pool of acyl?acyl carrier proteins (ACPs) an acyl chain of a specific length for covalent linkage to the protoxin. The acyltransferase also selects whether both or only one of two conserved lysine residues of the protoxin will be posttranslationally acylated. Functional assays revealed that RtxA has to be modified by 14-carbon fatty acyl chains to be biologically active, that HlyA remains active also when modified by 16-carbon acyl chains, and that CyaA is activated exclusively by 16-carbon acyl chains. These results suggest that the RTX toxin molecules are structurally adapted to the length of the acyl chains used for modification of their acylated lysine residue in the second, more conserved acylation site.
ER  -

OSICKOVA, Adriana; Humaira KHALIQ; Jiri MASIN; David JURNECKA; Anna SUKOVA; Radovan FISER; Jana HOLUBOVA; Ondrej STANEK; Peter SEBO and Radim OSICKA. Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins. \textit{International Journal of Biological Chemistry}. AMSTERDAM: ANSInet, 2020, vol.~295, No~28, p.~9268-9280. ISSN~1819-155X. Available from: https://doi.org/10.1074/jbc.RA120.014122.

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