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Yersinia pseudotuberculosis cytotoxic necrotizing factor interacts with glycosaminoglycans
Author(s) -
Kowarschik Stefanie,
Schöllkopf Julian,
Müller Thomas,
Tian Songhai,
Knerr Julian,
Bakker Hans,
Rein Stephan,
Dong Min,
Weber Stefan,
Grosse Robert,
Schmidt Gudula
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001630r
Subject(s) - yersinia pseudotuberculosis , endosome , heparan sulfate , chemistry , microbiology and biotechnology , yersinia , cytotoxic t cell , glycosaminoglycan , biochemistry , cell , biology , bacteria , in vitro , genetics , virulence , gene
The Cytotoxic Necrotizing Factor Y (CNFY) is produced by the gram‐negative, enteric pathogen Yersinia pseudotuberculosis . The bacterial toxin belongs to a family of deamidases, which constitutively activate Rho GTPases, thereby balancing inflammatory processes. We identified heparan sulfate proteoglycans as essential host cell factors for intoxication with CNFY. Using flow cytometry, microscopy, knockout cell lines, pulsed electron–electron double resonance, and bio‐layer interferometry, we studied the role of glucosaminoglycans in the intoxication process of CNFY. Especially the C‐terminal part of CNFY, which encompasses the catalytic activity, binds with high affinity to heparan sulfates. CNFY binding with the N‐terminal domain to a hypothetical protein receptor may support the interaction between the C‐terminal domain and heparan sulfates, which seems sterically hindered in the full toxin. A second conformational change occurs by acidification of the endosome, probably allowing insertion of the hydrophobic regions of the toxin into the endosomal membrane. Our findings suggest that heparan sulfates play a major role for intoxication within the endosome, rather than being relevant for an interaction at the cell surface.