EMD-13378
Full-length cryo-EM structure of the native human uromodulin (UMOD)/Tamm-Horsfall protein (THP) filament
EMD-13378
Single-particle6.1 Å
Deposition: 11/08/2021Map released: 16/03/2022
Last modified: 16/10/2024
Sample Organism:
Homo sapiens
Sample: Uromodulin (UMOD)/Tamm-Horsfall protein (THP)
Fitted models: 7pfp (Avg. Q-score: 0.182)
Deposition Authors: Jovine L
,
Xu C
Sample: Uromodulin (UMOD)/Tamm-Horsfall protein (THP)
Fitted models: 7pfp (Avg. Q-score: 0.182)
Deposition Authors: Jovine L
,
Xu C
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
(2022) Nat Struct Mol Biol , 29 , 190 - 193
,
Han L ,
Yamakawa N ,
Carroni M,
Tunyasuvunakool K,
Jumper J ,
de Sanctis D ,
Wu B ,
Jovine L
(2022) Nat Struct Mol Biol , 29 , 190 - 193
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.
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.
Secondary citations:
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- Yang H, Wu C, Zhao S & Guo J. (2004) Identification and characterization of D8C, a novel domain present in liver-specific LZP, uromodulin and glycoprotein 2, mutated in familial juvenile hyperuricaemic nephropathy. FEBS Lett, 578, 236 - 238
- Schaeffer C, Santambrogio S, Perucca S, Casari G & Rampoldi L. (2009) Analysis of uromodulin polymerization provides new insights into the mechanisms regulating ZP domain-mediated protein assembly. Mol Biol Cell, 20, 589 - 599
- Brunati M, Perucca S, Han L, Cattaneo A, Consolato F, Andolfo A, Schaeffer C, Olinger E, Peng J, Santambrogio S, Perrier R, Li S, Bokhove M, Bachi A, Hummler E, Devuyst O, Wu Q, Jovine L & Rampoldi L. (2015) The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin. eLife, 4, e08887
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