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

Stsiapanava A, Xu C, Nishio S, Han L, Yamakawa N, Carroni M, Tunyasuvunakool K, Jumper J, de Sanctis D, Wu B, Jovine L

Nat. Struct. Mol. Biol. 29 (3) 190-193 [2022-03-00; online 2022-03-10]

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.

Cryo-EM [Collaborative]

PubMed 35273390

DOI 10.1038/s41594-022-00729-3

Crossref 10.1038/s41594-022-00729-3

pii: 10.1038/s41594-022-00729-3

Publications 7.1.2