7Q3N

Cryo-EM of the complex between human uromodulin (UMOD)/Tamm-Horsfall protein (THP) and the FimH lectin domain from uropathogenic E. coli

Summary for 7Q3N

• Entry DOI: 10.2210/pdb7q3n/pdb
• Related: 6GTW 6TQK 7PFP
• EMDB information: 10553 13378 13794
• Descriptor: Uromodulin, Type 1 fimbiral adhesin FimH, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: egf domain, decoy module, beta-hairpin, d10c domain, d8c domain, extracellular matrix, glycoprotein, n-glycan, high-mannose sugar, cell adhesion, antimicrobial protein, bacterial adhesin, type i pilus, sugar binding protein, lectin, urinary tract infection, uti, uropathogenic e. coli, upec
• Biological source: Escherichia coli (strain UTI89 / UPEC); More
• Total number of polymer chains: 2
• Total formula weight: 83877.90

Authors

Jovine, L.,Xu, C.,Stsiapanava, A.,Carroni, M.,Tunyasuvunakool, K.,Jumper, J.,Wu, B. (deposition date: 2021-10-28, release date: 2022-03-16, Last modification date: 2024-10-23)

Primary citation

Stsiapanava, A.,Xu, C.,Nishio, S.,Han, L.,Yamakawa, N.,Carroni, M.,Tunyasuvunakool, K.,Jumper, J.,de Sanctis, D.,Wu, B.,Jovine, L.
Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH.
Nat.Struct.Mol.Biol., 29:190-193, 2022

PubMed 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.

PubMed: 35273390
DOI: 10.1038/s41594-022-00729-3

Experimental method

ELECTRON MICROSCOPY (7.4 Å)