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

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.
Alena Stsiapanava 1,  Chenrui Xu 2 3,  Shunsuke Nishio 1,  Ling Han 1,  Nao Yamakawa 4,  Marta Carroni 5,  Kathryn Tunyasuvunakool 6,  John Jumper 6,  Daniele de Sanctis 7,  Bin Wu 2 3,  Luca Jovine 8 9
Affiliations

Affiliations

  • 1 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
  • 2 School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
  • 3 NTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore.
  • 4 US 41-UMS 2014-PLBS, Université de Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Lille, France.
  • 5 Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
  • 6 DeepMind, London, UK.
  • 7 ESRF - The European Synchrotron, Grenoble, France.
  • 8 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. luca.jovine@ki.se.
  • 9 School of Biological Sciences, Nanyang Technological University, Singapore, Singapore. luca.jovine@ki.se.
PMID: 35273390 DOI: 10.1038/s41594-022-00729-3
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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