F. Xavier Gomis‐Rüth
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View article: Correction: Biochemical and structural characterization of the human gut microbiome metallopeptidase IgAse provides insight into its unique specificity for the Fab’ region of IgA1 and IgA2
Correction: Biochemical and structural characterization of the human gut microbiome metallopeptidase IgAse provides insight into its unique specificity for the Fab’ region of IgA1 and IgA2 Open
[This corrects the article DOI: 10.1371/journal.ppat.1013292.].
View article: Biochemical and structural characterization of the human gut microbiome metallopeptidase IgAse provides insight into its unique specificity for the Fab' region of IgA1 and IgA2.
Biochemical and structural characterization of the human gut microbiome metallopeptidase IgAse provides insight into its unique specificity for the Fab' region of IgA1 and IgA2. Open
Human immunoglobulin A (IgA), comprising the isotypes IgA1 and IgA2, protects ~400 m2 of mucosal surfaces against microbial infections but can also lead to aberrant IgA deposits that cause disease. Certain bacteria have evolved peptidases …
View article: Structural and functional insights into the C-terminal signal domain of the Bacteroidetes type-IX secretion system
Structural and functional insights into the C-terminal signal domain of the Bacteroidetes type-IX secretion system Open
Gram-negative bacteria from the Bacteroidota phylum possess a type-IX secretion system (T9SS) for protein secretion, which requires cargoes to have a C-terminal domain (CTD). Structurally analysed CTDs are from Porphyromonas gingivalis pro…
View article: Domain collapse and active site ablation generate a widespread animal mitochondrial seryl-tRNA synthetase
Domain collapse and active site ablation generate a widespread animal mitochondrial seryl-tRNA synthetase Open
Through their aminoacylation reactions, aminoacyl tRNA-synthetases (aaRS) establish the rules of the genetic code throughout all of nature. During their long evolution in eukaryotes, additional domains and splice variants were added to wha…
View article: Structural and evolutionary insights into astacin metallopeptidases
Structural and evolutionary insights into astacin metallopeptidases Open
The astacins are a family of metallopeptidases (MPs) that has been extensively described from animals. They are multidomain extracellular proteins, which have a conserved core architecture encompassing a signal peptide for secretion, a pro…
View article: Structural insights into latency of the metallopeptidase ulilysin (lysargiNase) and its unexpected inhibition by a sulfonyl–fluoride inhibitor of serine peptidases
Structural insights into latency of the metallopeptidase ulilysin (lysargiNase) and its unexpected inhibition by a sulfonyl–fluoride inhibitor of serine peptidases Open
The metallopeptidase ulilysin is kept latent by a cysteine-switch mechanism and is unexpectedly inhibited by the serine-peptidase inhibitor, 4-(2-aminoethyl)benzenesulfonyl fluoride.
View article: A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen <i>Tannerella forsythia</i>
A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen <i>Tannerella forsythia</i> Open
Periodontopathogenic Tannerella forsythia possesses the unique, tightly-regulated KLIKK-peptidase/potempin system in which six distinct metallo- and serine peptidases are specifically inhibited by cognate potempins (Pot) A, B1, B2, C, D an…
View article: Zymogenic latency in an ∼250-million-year-old astacin metallopeptidase
Zymogenic latency in an ∼250-million-year-old astacin metallopeptidase Open
The horseshoe crab Limulus polyphemus is one of few extant Limulus species, which date back to ∼250 million years ago under the conservation of a common Bauplan documented by fossil records. It possesses the only proteolytic blood-coagulat…
View article: Repositioning small molecule drugs as allosteric inhibitors of the BFT‐3 toxin from enterotoxigenic <i>Bacteroides fragilis</i>
Repositioning small molecule drugs as allosteric inhibitors of the BFT‐3 toxin from enterotoxigenic <i>Bacteroides fragilis</i> Open
Bacteroides fragilis is an abundant commensal component of the healthy human colon. However, under dysbiotic conditions, enterotoxigenic B. fragilis (ETBF) may arise and elicit diarrhea, anaerobic bacteremia, inflammatory bowel disease, an…
View article: Reply to Harwood et al.: Alternative functional conformations of native human α <sub>2</sub> -macroglobulin
Reply to Harwood et al.: Alternative functional conformations of native human α <sub>2</sub> -macroglobulin Open
Harwood et al. (1) challenge our study of human α2-macroglobulin (hα2M) by cryogenic electron microscopy (2) based on differences with other α2M-family members. This discrepancy would result from damaged protein caused by the usage of thaw…
View article: Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human α<sub>2</sub>-macroglobulin
Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human α<sub>2</sub>-macroglobulin Open
Human α 2 -macroglobulin (hα 2 M) is a multidomain protein with a plethora of essential functions, including transport of signaling molecules and endopeptidase inhibition in innate immunity. Here, we dissected the molecular mechanism of th…
View article: De Novo Design of Immunoglobulin-like Domains
De Novo Design of Immunoglobulin-like Domains Open
Antibodies and antibody derivatives such as nanobodies contain immunoglobulin-like (Ig) β-sandwich scaffolds which anchor the hypervariable antigen-binding loops and constitute the largest growing class of drugs. Current engineering strate…
View article: Intermolecular latency regulates the essential C-terminal signal peptidase and sortase of the <i>Porphyromonas gingivalis</i> type-IX secretion system
Intermolecular latency regulates the essential C-terminal signal peptidase and sortase of the <i>Porphyromonas gingivalis</i> type-IX secretion system Open
Significance Selected gram-negative bacteria employ a type-IX secretion system to shuttle virulence proteins with a C-terminal domain (CTD) as a secretion signal across the outer membrane. Upon secretion, the CTD is cleaved and replaced wi…
View article: The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin β by endogenous fetuin-B
The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin β by endogenous fetuin-B Open
Significance Membrane-bound metallopeptidases cut substrates as “sheddases” on the cell surface. Due to the irreversibility of peptide bond cleavage, they are regulated by specific, colocalizing protein inhibitors. We solved the crystal st…
View article: PorZ, an Essential Component of the Type IX Secretion System of <i>Porphyromonas gingivalis</i> , Delivers Anionic Lipopolysaccharide to the PorU Sortase for Transpeptidase Processing of T9SS Cargo Proteins
PorZ, an Essential Component of the Type IX Secretion System of <i>Porphyromonas gingivalis</i> , Delivers Anionic Lipopolysaccharide to the PorU Sortase for Transpeptidase Processing of T9SS Cargo Proteins Open
Bacteria have evolved multiple systems to transport effector proteins to their surface or into the surrounding milieu. These proteins have a wide range of functions, including attachment, motility, nutrient acquisition, and toxicity in the…
View article: The essential<i>Porphyromonas gingivalis</i>type IX secretion system component PorZ delivers anionic-lipopolysaccharide to the PorU sortase for transpeptidase processing of cargos
The essential<i>Porphyromonas gingivalis</i>type IX secretion system component PorZ delivers anionic-lipopolysaccharide to the PorU sortase for transpeptidase processing of cargos Open
Cargo proteins of the type IX secretion system (T9SS) in human pathogens from phylum Bacteroidetes invariably possess a conserved C-terminal domain (CTD) that functions as a signal for outer membrane (OM) translocation. In Porphyromonas gi…
View article: Analysis of the inhibiting activity of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) on matrix metalloproteinases
Analysis of the inhibiting activity of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) on matrix metalloproteinases Open
Matrix metalloproteinases (MMPs) occur in 23 human paralogues with key functions in physiology, and their activity is controlled by protein inhibitors. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), which is essential f…
View article: Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases
Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases Open
Tannerella forsythia is an oral dysbiotic periodontopathogen involved in severe human periodontal disease. As part of its virulence factor armamentarium, at the site of colonization it secretes mirolysin, a metallopeptidase of the unicellu…
View article: The C-terminal region of human plasma fetuin-B is dispensable for the raised-elephant-trunk mechanism of inhibition of astacin metallopeptidases
The C-terminal region of human plasma fetuin-B is dispensable for the raised-elephant-trunk mechanism of inhibition of astacin metallopeptidases Open
Human fetuin-B plays a key physiological role in human fertility through its inhibitory action on ovastacin, a member of the astacin family of metallopeptidases. The inhibitor consists of tandem cystatin-like domains (CY1 and CY2), which a…
View article: Recombinant production, purification, crystallization, and structure analysis of human transforming growth factor β2 in a new conformation
Recombinant production, purification, crystallization, and structure analysis of human transforming growth factor β2 in a new conformation Open
Transforming growth factor β is a disulfide-linked dimeric cytokine that occurs in three highly related isoforms (TGFβ1–TGFβ3) engaged in signaling functions through binding of cognate TGFβ receptors. To regulate this pathway, the cytokine…
View article: Structural determinants of inhibition of Porphyromonas gingivalis gingipain K by KYT-36, a potent, selective, and bioavailable peptidase inhibitor
Structural determinants of inhibition of Porphyromonas gingivalis gingipain K by KYT-36, a potent, selective, and bioavailable peptidase inhibitor Open
Porphyromonas gingivalis is a member of the dysbiotic oral microbiome and a “keystone pathogen” that causes severe periodontal disease, which is among the most prevalent infectious diseases. Part of the virulence factors secreted by P. gin…