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Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH

Nat Struct Mol Biol. 2022-03; 
Alena Stsiapanava, Chenrui Xu, Shunsuke Nishio, Ling Han, Nao Yamakawa, Marta Carroni, Kathryn Tunyasuvunakool, John Jumper, Daniele de Sanctis, Bin Wu, Luca Jovine
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Mutant Libraries … A corresponding gene and an equivalent UMOD construct, as well as GP2 Δ31-59, Δ31-88 and N65A mutant genes, were also synthesized (GenScript) and all constructs were cloned … Get A Quote

摘要

Glycoprotein 2 (GP2) and uromodulin (UMOD) filaments protect against gastrointestinal and urinary tract infections by acting as decoys for bacterial fimbrial lectin FimH. By combining AlphaFold2 predictions with X-ray crystallography and cryo-EM, we show that these proteins contain a bipartite decoy module whose new fold presents the high-mannose glycan recognized by FimH. The structure rationalizes UMOD mutations associated with kidney diseases and visualizes a key epitope implicated in cast nephropathy.

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