6SJX

Precursor structure of the self-processing module of iron-regulated FrpC of N. Meningitidis with calcium ions

Summary for 6SJX

• Entry DOI: 10.2210/pdb6sjx/pdb
• NMR Information: BMRB: 26530,34424
• Descriptor: Iron-regulated protein FrpC, CALCIUM ION (2 entities in total)
• Functional Keywords: repeat in toxin proteins, calcium, metal binding protein
• Biological source: Neisseria meningitidis serogroup C
• Total number of polymer chains: 1
• Total formula weight: 19447.27

Authors

Kuban, V.,Macek, P.,Hritz, J.,Nechvatalova, K.,Nedbalcova, K.,Faldyna, M.,Zidek, L.,Bumba, L. (deposition date: 2019-08-14, release date: 2020-02-26, Last modification date: 2024-06-19)

Primary citation

Kuban, V.,Macek, P.,Hritz, J.,Nechvatalova, K.,Nedbalcova, K.,Faldyna, M.,Sebo, P.,Zidek, L.,Bumba, L.
Structural Basis of Ca 2+ -Dependent Self-Processing Activity of Repeat-in-Toxin Proteins.
Mbio, 11:-, 2020

PubMed Abstract: The posttranslational Ca-dependent "clip-and-link" activity of large epeat-in-oin (RTX) proteins starts by Ca-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 ε-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 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 attenuated the virulence of this porcine pathogen in a pig respiratory challenge model. We hypothesize that the Ca-dependent clip-and-link activity represents an unconventional strategy for Gram-negative pathogens to adhere to the host target cell surface. The Ca-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 Ca-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 Ca-loaded SPM (Ca-SPM) defining the mechanism of the autocatalytic cleavage of the Asp414-Pro415 peptide bond of the FrpC exoprotein. Moreover, deletion of the SPM domain in the ApxIVA protein, the FrpC homolog of , resulted in attenuation of virulence of the bacterium in a pig infection model, indicating that the Ca-dependent clip-and-link activity plays a role in the virulence of Gram-negative pathogens.

PubMed: 32184239
DOI: 10.1128/mBio.00226-20

Experimental method

SOLUTION NMR