Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
Alena Stsiapanava(Karolinska Institutet), Chenrui Xu(Nanyang Technological University), Shunsuke Nishio(Karolinska Institutet), Ling Han(Karolinska Institutet), Nao Yamakawa(Centre National de la Recherche Scientifique), Marta Carroni(Stockholm University), Kathryn Tunyasuvunakool(Google DeepMind (United Kingdom)), John Jumper(Google DeepMind (United Kingdom)), Daniele de Sanctis(European Synchrotron Radiation Facility), Bin Wu(Nanyang Technological University), Luca Jovine(Nanyang Technological University)
Cited by 31Open Access
Abstract
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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