7PFP

Full-length cryo-EM structure of the native human uromodulin (UMOD)/Tamm-Horsfall protein (THP) filament

Summary for 7PFP

• Entry DOI: 10.2210/pdb7pfp/pdb
• Related: 4WRN 6TQK 6TQL 7P6R 7P6S 7P6T
• EMDB information: 10553 10554 13378
• Descriptor: Uromodulin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: egf domain, decoy module, beta-hairpin, d10c domain, zp module, zp domain, zp-n domain, zp-c domain, interdomain linker, extracellular matrix, glycoprotein, n-glycan, structural protein, protein filament, protein polymerization, antimicrobial protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 224801.05

Authors

Jovine, L.,Xu, C.,Stsiapanava, A.,Carroni, M.,Tunyasuvunakool, K.,Jumper, J.,Wu, B. (deposition date: 2021-08-11, release date: 2022-03-16, Last modification date: 2024-10-16)

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 (6.1 Å)