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Crystal structure of enterohemorrhagic E. coli StcECrystal structure of enterohemorrhagic E. coli StcE
Structural highlights
FunctionSTCE_ECO57 Virulence factor that contributes to intimate adherence of enterohemorrhagic E.coli (EHEC) O157:H7 to host cells. Is able to cleave the secreted human mucin 7 (MUC7) and the glycoprotein 340 (DMBT1/GP340). Also cleaves human C1 inhibitor (SERPING1), a regulator of multiple inflammatory pathways, and binds and localizes it to bacterial and host cell surfaces, protecting them from complement-mediated lysis. Therefore, the current model proposes two roles for StcE during infection: it acts first as a mucinase, allowing passage of EHEC through the oral cavity by cleaving the salivary glycoproteins that are responsible for bacterial aggregation. Similarly, in the colon, StcE cleaves the glycoproteins that protect the intestinal epithelial surface, allowing EHEC to come into close contact with host cell membranes. Secondly, it acts as an anti-inflammatory agent by localizing SERPING1 to cell membranes.[1] [2] [3] [4] Publication Abstract from PubMedMucin glycoproteins with large numbers of O-linked glycosylations comprise the mucosal barrier lining the mammalian gastrointestinal tract from mouth to gut. A critical biological function of mucins is to protect the underlying epithelium from infection. Enterohemorrhagic Escherichia coli (EHEC), the mediator of severe food- and water-borne disease, can breach this barrier and adhere to intestinal cells. StcE, a approximately 100 kDa metalloprotease secreted by EHEC, plays a pivotal role in remodeling the mucosal lining during infection. To obtain mechanistic insight into its function, we have determined the structure of StcE. Our data reveal a dynamic, multidomain architecture featuring an unusually large substrate-binding cleft and a prominent polarized surface charge distribution highly suggestive of an electrostatic role in substrate targeting. The observation of key conserved motifs in the active site allows us to propose the structural basis for the specific recognition of alpha-O-glycan-containing substrates. Complementary biochemical analysis provides further insight into its distinct substrate specificity and binding stoichiometry. Structural insight into the bacterial mucinase StcE essential to adhesion and immune evasion during enterohemorrhagic E. coli infection.,Yu AC, Worrall LJ, Strynadka NC Structure. 2012 Apr 4;20(4):707-17. Epub 2012 Apr 3. PMID:22483117[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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