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  1. Article ; Online: Modification of the RTX domain cap by acyl chains of adapted length rules the formation of functional hemolysin pores.

    Lepesheva, Anna / Grobarcikova, Michaela / Osickova, Adriana / Jurnecka, David / Knoblochova, Sarka / Cizkova, Monika / Osicka, Radim / Sebo, Peter / Masin, Jiri

    Biochimica et biophysica acta. Biomembranes

    2024  Volume 1866, Issue 5, Page(s) 184311

    Abstract: The acylated pore-forming Repeats in ToXin (RTX) cytolysins α-hemolysin (HlyA) and adenylate cyclase toxin (CyaA) preferentially bind to ... ...

    Abstract The acylated pore-forming Repeats in ToXin (RTX) cytolysins α-hemolysin (HlyA) and adenylate cyclase toxin (CyaA) preferentially bind to β
    Language English
    Publishing date 2024-04-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 60-7
    ISSN 1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamem.2024.184311
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The adenylate cyclase toxin RTX domain follows a series templated folding mechanism with implications for toxin activity.

    Chen, Guojun / Wang, Han / Bumba, Ladislav / Masin, Jiri / Sebo, Peter / Li, Hongbin

    The Journal of biological chemistry

    2023  Volume 299, Issue 9, Page(s) 105150

    Abstract: Folding of the Repeats-in-toxin (RTX) domain of the bacterial adenylate cyclase toxin-hemolysin (CyaA) is critical to its toxin activities and the virulence of the whooping cough agent Bordetella pertussis. The RTX domain (RD) contains five RTX blocks ( ... ...

    Abstract Folding of the Repeats-in-toxin (RTX) domain of the bacterial adenylate cyclase toxin-hemolysin (CyaA) is critical to its toxin activities and the virulence of the whooping cough agent Bordetella pertussis. The RTX domain (RD) contains five RTX blocks (RTX-i to RTX-v) and their folding is driven by the binding of calcium. However, the detailed molecular mechanism via which the folding signal transmits within the five RTX blocks remains unknown. By combining single molecule optical tweezers, protein engineering, and toxin activity assays, here we demonstrate that the folding of the RD follows a strict hierarchy, with the folding starting from its C-terminal block RTX-v and proceeding towards the N-terminal RTX-i block sequentially. Our results reveal a strict series, templated folding mechanism, where the folding signal is transmitted along the RD in a series fashion from its C terminus continuously to the N terminus. Due to the series nature of this folding signal transmission pathway, the folding of RD can be disrupted at any given RTX block, rendering the RTX blocks located N-terminally to the disruption site and the acylation region of CyaA unfolded and abolishing CyaA's toxin activities. Our results reveal key mechanistic insights into the secretion and folding process of CyaA and may open up new potential avenues towards designing new therapeutics to abolish toxin activity of CyaA and combat B. pertussis.
    Language English
    Publishing date 2023-08-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2023.105150
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Phospholipase A activity of adenylate cyclase toxin?

    Masin, Jiri / Osicka, Radim / Bumba, Ladislav / Sebo, Peter

    Proceedings of the National Academy of Sciences of the United States of America

    2018  Volume 115, Issue 11, Page(s) E2489–E2490

    MeSH term(s) Adenylate Cyclase Toxin ; Adenylyl Cyclases ; Cholera Toxin ; Enzyme Activation ; Pertussis Toxin ; Phospholipases ; Virulence Factors, Bordetella
    Chemical Substances Adenylate Cyclase Toxin ; Virulence Factors, Bordetella ; Cholera Toxin (9012-63-9) ; Pertussis Toxin (EC 2.4.2.31) ; Phospholipases (EC 3.1.-) ; Adenylyl Cyclases (EC 4.6.1.1)
    Language English
    Publishing date 2018-02-21
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1722588115
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme-translocating segment of

    Masin, Jiri / Osickova, Adriana / Jurnecka, David / Klimova, Nela / Khaliq, Humaira / Sebo, Peter / Osicka, Radim

    The Journal of biological chemistry

    2020  Volume 295, Issue 28, Page(s) 9349–9365

    Abstract: ... ...

    Abstract The
    MeSH term(s) Adenylate Cyclase Toxin/metabolism ; Animals ; Bordetella ; CHO Cells ; Cricetulus ; Cytosol/metabolism ; Female ; Humans ; Jurkat Cells ; Lymphocyte Function-Associated Antigen-1/metabolism ; Macrophage-1 Antigen/metabolism ; Mice ; Mice, Inbred BALB C ; Protein Transport ; THP-1 Cells
    Chemical Substances Adenylate Cyclase Toxin ; Lymphocyte Function-Associated Antigen-1 ; Macrophage-1 Antigen
    Language English
    Publishing date 2020-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA120.013630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A conserved tryptophan in the acylated segment of RTX toxins controls their β

    Osickova, Adriana / Knoblochova, Sarka / Bumba, Ladislav / Man, Petr / Kalaninova, Zuzana / Lepesheva, Anna / Jurnecka, David / Cizkova, Monika / Biedermannova, Lada / Goldsmith, Jory A / Maynard, Jennifer A / McLellan, Jason S / Osicka, Radim / Sebo, Peter / Masin, Jiri

    The Journal of biological chemistry

    2023  Volume 299, Issue 8, Page(s) 104978

    Abstract: The acylated Repeats in ToXins (RTX) leukotoxins, the adenylate cyclase toxin (CyaA) or α-hemolysin (HlyA), bind ... ...

    Abstract The acylated Repeats in ToXins (RTX) leukotoxins, the adenylate cyclase toxin (CyaA) or α-hemolysin (HlyA), bind β
    MeSH term(s) Adenylate Cyclase Toxin/chemistry ; Adenylate Cyclase Toxin/genetics ; Adenylate Cyclase Toxin/metabolism ; Bordetella pertussis ; CD18 Antigens/genetics ; CD18 Antigens/metabolism ; Cell Membrane/metabolism ; Erythrocytes/metabolism ; Tryptophan/chemistry ; Tryptophan/genetics ; Tryptophan/metabolism ; Conserved Sequence
    Chemical Substances Adenylate Cyclase Toxin ; CD18 Antigens ; Tryptophan (8DUH1N11BX)
    Language English
    Publishing date 2023-06-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2023.104978
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Selective Enhancement of the Cell-Permeabilizing Activity of Adenylate Cyclase Toxin Does Not Increase Virulence of

    Holubova, Jana / Juhasz, Attila / Masin, Jiri / Stanek, Ondrej / Jurnecka, David / Osickova, Adriana / Sebo, Peter / Osicka, Radim

    International journal of molecular sciences

    2021  Volume 22, Issue 21

    Abstract: The whooping cough agent, ...

    Abstract The whooping cough agent,
    MeSH term(s) Adenylate Cyclase Toxin/metabolism ; Animals ; Bordetella pertussis/pathogenicity ; Bordetella pertussis/physiology ; Cell Membrane Permeability ; Cyclic AMP/metabolism ; Female ; Host-Pathogen Interactions ; Humans ; Mice ; Mice, Inbred BALB C ; Phagocytes/metabolism ; Phagocytes/microbiology ; Sheep ; Virulence ; Whooping Cough/metabolism ; Whooping Cough/microbiology ; Whooping Cough/pathology
    Chemical Substances Adenylate Cyclase Toxin ; Cyclic AMP (E0399OZS9N)
    Language English
    Publishing date 2021-10-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222111655
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Bordetella Pertussis

    Bumba, Ladislav / Masin, Jiri / Osickova, Adriana / Osicka, Radim / Sebo, Peter

    Toxins

    2018  Volume 10, Issue 6

    Abstract: The adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) plays a crucial role in virulence and airway colonization capacity of the whooping cough ... ...

    Abstract The adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) plays a crucial role in virulence and airway colonization capacity of the whooping cough agent
    MeSH term(s) Adenylate Cyclase Toxin/metabolism ; Adenylate Cyclase Toxin/toxicity ; Animals ; Aspartic Acid ; Bordetella pertussis ; Cell Line ; Erythrocytes ; Hemolysis ; Mice ; Phospholipases A/metabolism ; Serine ; Sheep
    Chemical Substances Adenylate Cyclase Toxin ; Aspartic Acid (30KYC7MIAI) ; Serine (452VLY9402) ; Phospholipases A (EC 3.1.1.32)
    Language English
    Publishing date 2018-06-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins10060245
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Almost half of the RTX domain is dispensable for complement receptor 3 binding and cell-invasive activity of the Bordetella adenylate cyclase toxin.

    Espinosa-Vinals, Carlos Angel / Masin, Jiri / Holubova, Jana / Stanek, Ondrej / Jurnecka, David / Osicka, Radim / Sebo, Peter / Bumba, Ladislav

    The Journal of biological chemistry

    2021  Volume 297, Issue 1, Page(s) 100833

    Abstract: The whooping cough agent Bordetella pertussis secretes an adenylate cyclase toxin (CyaA) that through its large carboxy-proximal Repeat-in-ToXin (RTX) domain binds the complement receptor 3 (CR3). The RTX domain consists of five blocks (I-V) of ... ...

    Abstract The whooping cough agent Bordetella pertussis secretes an adenylate cyclase toxin (CyaA) that through its large carboxy-proximal Repeat-in-ToXin (RTX) domain binds the complement receptor 3 (CR3). The RTX domain consists of five blocks (I-V) of characteristic glycine and aspartate-rich nonapeptides that fold into five Ca
    MeSH term(s) Acylation ; Adenylate Cyclase Toxin/metabolism ; Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/metabolism ; Bordetella pertussis/pathogenicity ; CHO Cells ; Calcium/metabolism ; Cricetulus ; Epitopes/metabolism ; Humans ; Macrophage-1 Antigen/chemistry ; Macrophage-1 Antigen/metabolism ; Protein Binding ; Protein Domains ; Protein Folding ; Structure-Activity Relationship ; THP-1 Cells
    Chemical Substances Adenylate Cyclase Toxin ; Antibodies, Neutralizing ; Epitopes ; Macrophage-1 Antigen ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2021-05-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2021.100833
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  9. Article ; Online: Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins.

    Osickova, Adriana / Khaliq, Humaira / Masin, Jiri / Jurnecka, David / Sukova, Anna / Fiser, Radovan / Holubova, Jana / Stanek, Ondrej / Sebo, Peter / Osicka, Radim

    The Journal of biological chemistry

    2020  Volume 295, Issue 28, Page(s) 9268–9280

    Abstract: In a wide range of organisms, from bacteria to humans, numerous proteins have to be posttranslationally acylated to become biologically active. ... ...

    Abstract In a wide range of organisms, from bacteria to humans, numerous proteins have to be posttranslationally acylated to become biologically active. Bacterial
    MeSH term(s) Acyltransferases/metabolism ; Animals ; Bacteria/metabolism ; Bacterial Proteins/metabolism ; Cell Line ; Fatty Acids/metabolism ; Hemolysin Proteins/metabolism ; Mice
    Chemical Substances Bacterial Proteins ; Fatty Acids ; Hemolysin Proteins ; Acyltransferases (EC 2.3.-)
    Language English
    Publishing date 2020-05-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA120.014122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Rapid Purification of Endotoxin-Free RTX Toxins.

    Stanek, Ondrej / Masin, Jiri / Osicka, Radim / Jurnecka, David / Osickova, Adriana / Sebo, Peter

    Toxins

    2019  Volume 11, Issue 6

    Abstract: Cytolytic leukotoxins of the repeat in toxin (RTX) family are large proteins excreted by gram-negative bacterial pathogens through the type 1 secretion system (T1SS). Due to low yields and poor stability in cultures of the original pathogens, it is ... ...

    Abstract Cytolytic leukotoxins of the repeat in toxin (RTX) family are large proteins excreted by gram-negative bacterial pathogens through the type 1 secretion system (T1SS). Due to low yields and poor stability in cultures of the original pathogens, it is useful to purify recombinant fatty-acylated RTX cytolysins from inclusion bodies produced in
    MeSH term(s) Animals ; Bacterial Proteins/isolation & purification ; Bacterial Proteins/toxicity ; Cell Line, Tumor ; Cell Survival/drug effects ; Cytotoxins/isolation & purification ; Cytotoxins/toxicity ; Detergents/chemistry ; Erythrocytes/drug effects ; Escherichia coli/metabolism ; Hemolysin Proteins/isolation & purification ; Hemolysin Proteins/toxicity ; Hemolysis ; Humans ; Lipopolysaccharides/analysis ; Octoxynol/chemistry ; Sheep ; THP-1 Cells ; Urea/chemistry
    Chemical Substances Bacterial Proteins ; Cytotoxins ; Detergents ; Hemolysin Proteins ; Lipopolysaccharides ; Urea (8W8T17847W) ; Octoxynol (9002-93-1) ; Nonidet P-40 (9036-19-5)
    Language English
    Publishing date 2019-06-12
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins11060336
    Database MEDical Literature Analysis and Retrieval System OnLINE

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