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

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

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...

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Bibliographic Details
Main Authors: Stsiapanava, Alena, Xu, Chenrui, Nishio, Shunsuke, Han, Ling, Yamakawa, Nao, Carroni, Marta, Tunyasuvunakool, Kathryn, Jumper, John, de Sanctis, Daniele, Wu, Bin, Jovine, Luca
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2022
Subjects:
Science::Biological sciences
Cryo-EM
Structure Refinement
Online Access:https://hdl.handle.net/10356/162976
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Institution: Nanyang Technological University
Language: English
Description
Summary: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.

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