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

Nat Struct Mol Biol. 2022 Mar;29(3):190-193. doi: 10.1038/s41594-022-00729-3. Epub 2022 Mar 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial* / genetics
  • Crystallography, X-Ray
  • Fimbriae Proteins / chemistry
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism
  • Fimbriae, Bacterial* / chemistry
  • Fimbriae, Bacterial* / metabolism
  • GPI-Linked Proteins
  • Humans
  • Mannose / analysis
  • Uromodulin / analysis
  • Uromodulin / chemistry
  • Uromodulin / metabolism


  • Adhesins, Bacterial
  • GP2 protein, human
  • GPI-Linked Proteins
  • UMOD protein, human
  • Uromodulin
  • Fimbriae Proteins
  • Mannose