9gsm
From Proteopedia
Crystal structure of X409 complexed to tetra-core1-glycopeptide
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 PubMedThe mucus lining wet body surfaces forms the interphase and barrier for the microbiota and resident microbiomes. Large mucin proteins densely decorated with O-glycans make up the mucus lining to entrap, feed and shape the microbiota, and repress biofilm formation and virulence. How mucins exert these effects is poorly understood and critical is how the microbiota recognize, sense, and break down mucins. Here, we provide structural molecular evidence that a small mucin-binding module designated X409 recognizes clustered saccharide patches comprised of rows of inner monosaccharides in adjacent O-glycans. These patches are unique to mucins and binding to these provides an elegant mechanism to retain adherence to mucins despite trimming of O-glycans during microbial scavenging of monosaccharides from mucins. Realization of clustered saccharide patch-binding motifs provides a hitherto overlooked scenario of contextual glycan epitopes and impetus for discovery of new classes of glycan-binding proteins. Microbial binding module employs sophisticated clustered saccharide patches to selectively adhere to mucins.,Jaroentomeechai T, Veloz B, Soares CO, Goerdeler F, Grosso AS, Bull C, Miller RL, Furukawa S, Gines-Alcober I, Taleb V, Merino P, Ghirardello M, Companon I, Coelho H, Dias JS, Vincentelli R, Henrissat B, Joshi H, Clausen H, Corzana F, Marcelo F, Hurtado-Guerrero R, Narimatsu Y Nat Commun. 2025 Oct 13;16(1):9058. doi: 10.1038/s41467-025-63756-w. PMID:41083434[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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