Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
Alena Stsiapanava, Chenrui Xu, Shunsuke Nishio, Ling Han, Nao Yamakawa, Marta Carroni, Kathryn Tunyasuvunakool, John Jumper, Daniele de Sanctis, Bin Wu, Luca Jovine
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.
Topics & Concepts
Tamm–Horsfall proteinGlycoproteinDecoyGlycanLectinShigella dysenteriaeBiologyBacterial adhesinCell biologyEscherichia coliMicrobiologyComputational biologyGeneticsBiochemistryKidneyGeneReceptorEnzyme Structure and FunctionEscherichia coli research studiesPediatric Urology and Nephrology Studies