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

0524907 - MBÚ 2021 RIV US eng J - Článek v odborném periodiku
Kubáň, V. - Macek, P. - Hritz, J. - Nechvátalová, K. - Nedbalcová, K. - Faldyna, M. - Šebo, Peter - Zídek, L. - Bumba, Ladislav
Structural Basis of Ca2+-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins.
mBio. Roč. 11, č. 2 (2020), č. článku e00226-20. ISSN 2161-2129. E-ISSN 2150-7511
Grant CEP: GA ČR(CZ) GA19-15175S; GA MŠMT(CZ) LM2018133
Výzkumná infrastruktura: CIISB II - 90127; CESNET II - 90042
Institucionální podpora: RVO:61388971
Klíčová slova: RTX toxins * cell adhesion * clip-and-link
Obor OECD: Microbiology
Impakt faktor: 7.867, rok: 2020
Způsob publikování: Open access
https://mbio.asm.org/content/11/2/e00226-20

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.
Trvalý link: http://hdl.handle.net/11104/0309135