Structural Basis of Ca2+-Dependent Self-Processing Activity of
Repeat-in-Toxin Proteins

J 2020

Structural Basis of Ca2+-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins

KUBÁŇ, Vojtěch, P. MACEK, Jozef HRITZ, K. NECHVATALOVA, K. NEDBALCOVA et. al.

Základní údaje

Originální název

Structural Basis of Ca2+-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins

Autoři

KUBÁŇ, Vojtěch (203 Česká republika, domácí), P. MACEK, Jozef HRITZ (703 Slovensko, domácí), K. NECHVATALOVA, K. NEDBALCOVA, M. FALDYNA, Peter ŠEBO (203 Česká republika, domácí), Lukáš ŽÍDEK (203 Česká republika, garant, domácí) a L. BUMBA

Vydání

MBIO, Washington, D.C. American Society for Microbiology, 2020, 2150-7511

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10606 Microbiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.867

Kód RIV

RIV/00216224:14740/20:00115752

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1128/mBio.00226-20

UT WoS

000531071300056

Klíčová slova anglicky

RTX toxins; cell adhesion; clip-and-link; host-pathogen interactions; nuclear magnetic resonance

Štítky

CF NMR, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 14. 10. 2024 17:35, Ing. Jana Kuchtová

Anotace

V originále

The posttranslational Ca2+-dependent "clip-and-link" activity of large repeat-in-toxin (RTX) proteins starts by Ca2+-dependent structural rearrangement of a highly conserved self-processing module (SPM). Subsequently, an internal aspartate-proline (Asp-Pro) peptide bond at the N-terminal end of SPM breaks, and the liberated C-terminal aspartyl residue can react with a free epsilon-amino group of an adjacent lysine residue to form a new isopeptide bond. Here, we report a solution structure of the calcium-loaded SPM (Ca-SPM) derived from the FrpC protein of Neisseria meningitidis. The Ca-SPM structure defines a unique protein architecture and provides structural insight into the autocatalytic cleavage of the Asp-Pro peptide bond through a "twisted-amide" activation. Furthermore, in-frame deletion of the SPM domain from the ApxIVA protein of Actinobacillus pleuropneumoniae attenuated the virulence of this porcine pathogen in a pig respiratory challenge model. We hypothesize that the Ca2+-dependent clip-and-link activity represents an unconventional strategy for Gram-negative pathogens to adhere to the host target cell surface. IMPORTANCE The Ca2+-dependent clip-and-link activity of large repeat-in-toxin (RTX) proteins is an exceptional posttranslational process in which an internal domain called a self-processing module (SPM) mediates Ca2+ -dependent processing of a highly specific aspartate-proline (Asp-Pro) peptide bond and covalent linkage of the released aspartyl to an adjacent lysine residue through an isopeptide bond. Here, we report the solution structures of the Ca2+-loaded SPM (Ca-SPM) defining the mechanism of the autocatalytic cleavage of the Asp414-Pro415 peptide bond of the Neisseria meningitidis FrpC exoprotein. Moreover, deletion of the SPM domain in the ApxIVA protein, the FrpC homolog of Actinobacillus pleuropneumoniae, resulted in attenuation of virulence of the bacterium in a pig infection model, indicating that the Ca2+-dependent clip-and-link activity plays a role in the virulence of Gram-negative pathogens.

Návaznosti

LM2018133, projekt VaV

Název: Český národní uzel Evropské infrastruktury pro translační medicínu (Akronym: EATRIS-ERIC-CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Involvement of Czech Translational Medicine Infrastructure to the European Advanced Translational Research Infrastructure in Medicine

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

KUBÁŇ, Vojtěch, P. MACEK, Jozef HRITZ, K. NECHVATALOVA, K. NEDBALCOVA, M. FALDYNA, Peter ŠEBO, Lukáš ŽÍDEK a L. BUMBA. Structural Basis of Ca2+-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins. MBIO. Washington, D.C.: American Society for Microbiology, 2020, roč. 11, č. 2, s. 1-18. ISSN 2150-7511. Dostupné z: https://dx.doi.org/10.1128/mBio.00226-20.

@article{1660918,
   author = {Kubáň, Vojtěch and Macek, P. and Hritz, Jozef and Nechvatalova, K. and Nedbalcova, K. and Faldyna, M. and Šebo, Peter and Žídek, Lukáš and Bumba, L.},
   article_location = {Washington, D.C.},
   article_number = {2},
   doi = {http://dx.doi.org/10.1128/mBio.00226-20},
   keywords = {RTX toxins; cell adhesion; clip-and-link; host-pathogen interactions; nuclear magnetic resonance},
   language = {eng},
   issn = {2150-7511},
   journal = {MBIO},
   title = {Structural Basis of Ca2+-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins},
   url = {https://mbio.asm.org/content/mbio/11/2/e00226-20.full.pdf},
   volume = {11},
   year = {2020}
}

TY  - JOUR
ID  - 1660918
AU  - Kubáň, Vojtěch - Macek, P. - Hritz, Jozef - Nechvatalova, K. - Nedbalcova, K. - Faldyna, M. - Šebo, Peter - Žídek, Lukáš - Bumba, L.
PY  - 2020
TI  - Structural Basis of Ca2+-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins
JF  - MBIO
VL  - 11
IS  - 2
SP  - 1-18
EP  - 1-18
PB  - American Society for Microbiology
SN  - 21507511
KW  - RTX toxins
KW  - cell adhesion
KW  - clip-and-link
KW  - host-pathogen interactions
KW  - nuclear magnetic resonance
UR  - https://mbio.asm.org/content/mbio/11/2/e00226-20.full.pdf
L2  - https://mbio.asm.org/content/mbio/11/2/e00226-20.full.pdf
N2  - The posttranslational Ca2+-dependent "clip-and-link" activity of large repeat-in-toxin (RTX) proteins starts by Ca2+-dependent structural rearrangement of a highly conserved self-processing module (SPM). Subsequently, an internal aspartate-proline (Asp-Pro) peptide bond at the N-terminal end of SPM breaks, and the liberated C-terminal aspartyl residue can react with a free epsilon-amino group of an adjacent lysine residue to form a new isopeptide bond. Here, we report a solution structure of the calcium-loaded SPM (Ca-SPM) derived from the FrpC protein of Neisseria meningitidis. The Ca-SPM structure defines a unique protein architecture and provides structural insight into the autocatalytic cleavage of the Asp-Pro peptide bond through a "twisted-amide" activation. Furthermore, in-frame deletion of the SPM domain from the ApxIVA protein of Actinobacillus pleuropneumoniae attenuated the virulence of this porcine pathogen in a pig respiratory challenge model. We hypothesize that the Ca2+-dependent clip-and-link activity represents an unconventional strategy for Gram-negative pathogens to adhere to the host target cell surface. IMPORTANCE The Ca2+-dependent clip-and-link activity of large repeat-in-toxin (RTX) proteins is an exceptional posttranslational process in which an internal domain called a self-processing module (SPM) mediates Ca2+ -dependent processing of a highly specific aspartate-proline (Asp-Pro) peptide bond and covalent linkage of the released aspartyl to an adjacent lysine residue through an isopeptide bond. Here, we report the solution structures of the Ca2+-loaded SPM (Ca-SPM) defining the mechanism of the autocatalytic cleavage of the Asp414-Pro415 peptide bond of the Neisseria meningitidis FrpC exoprotein. Moreover, deletion of the SPM domain in the ApxIVA protein, the FrpC homolog of Actinobacillus pleuropneumoniae, resulted in attenuation of virulence of the bacterium in a pig infection model, indicating that the Ca2+-dependent clip-and-link activity plays a role in the virulence of Gram-negative pathogens.
ER  -

KUBÁŇ, Vojtěch, P. MACEK, Jozef HRITZ, K. NECHVATALOVA, K. NEDBALCOVA, M. FALDYNA, Peter ŠEBO, Lukáš ŽÍDEK a L. BUMBA. Structural Basis of Ca2+-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins. \textit{MBIO}. Washington, D.C.: American Society for Microbiology, 2020, roč.~11, č.~2, s.~1-18. ISSN~2150-7511. Dostupné z: https://dx.doi.org/10.1128/mBio.00226-20.

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