7q3n
From Proteopedia
Cryo-EM of the complex between human uromodulin (UMOD)/Tamm-Horsfall protein (THP) and the FimH lectin domain from uropathogenic E. coli
Structural highlights
DiseaseUROM_HUMAN UMOD-related autosomal dominant tubulointerstitial kidney disease. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionUROM_HUMAN Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water barrier permeability (Probable). May serve as a receptor for binding and endocytosis of cytokines (IL-1, IL-2) and TNF (PubMed:3498215). Facilitates neutrophil migration across renal epithelia (PubMed:20798515).[1] [2] In the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and inhibits formation of liquid containing supersaturated salts and subsequent formation of salt crystals.[UniProtKB:Q91X17] Publication Abstract from PubMedGlycoprotein 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. 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. 2022 Mar;29(3):190-193. doi: 10.1038/s41594-022-00729-3., Epub 2022 Mar 10. PMID:35273390[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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