6sjx

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

spinqualitylabelsall models 6sjx Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6sjx is a 1 chain structure with sequence from Neisseria meningitidis serogroup C. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FRPC_NEIMC May participate in the pathogenesis of meningococcal disease. Publication Abstract from PubMed The posttranslational Ca(2+)-dependent "clip-and-link" activity of large repeat-in-toxin (RTX) proteins starts by Ca(2+)-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 Ca(2+)-dependent clip-and-link activity represents an unconventional strategy for Gram-negative pathogens to adhere to the host target cell surface.IMPORTANCE The Ca(2+)-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(2+)-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(2+)-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 Ca(2+)-dependent clip-and-link activity plays a role in the virulence of Gram-negative pathogens. Structural Basis of Ca(2+)-Dependent Self-Processing Activity of Repeat-in-Toxin Proteins.,Kuban V, Macek P, Hritz J, Nechvatalova K, Nedbalcova K, Faldyna M, Sebo P, Zidek L, Bumba L mBio. 2020 Mar 17;11(2). pii: mBio.00226-20. doi: 10.1128/mBio.00226-20. PMID:32184239 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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