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

By A. Stsiapanava, Chenrui Xu, S. Nishio, Ling Han, Nao Yamakawa, M. Carroni, Kathryn Tunyasuvunakool, John M. Jumper, D. de Sanctis, Bin Wu and 1 more. 2022

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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. AlphaFold2 predictions, X-ray crystallography and cryo-EM analyses reveal how related human glycoproteins GP2 and uromodulin catch pathogenic bacteria by presenting a high-mannose glycan that acts as a decoy for fimbrial adhesin FimH.

Subfields: Endocrinology, Materials Chemistry, Pediatrics, Perinatology and Child Health