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


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.

SUBMITTER: Stsiapanava A 

PROVIDER: S-EPMC8930769 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Stsiapanava Alena A   Xu Chenrui C   Nishio Shunsuke S   Han Ling L   Yamakawa Nao N   Carroni Marta M   Tunyasuvunakool Kathryn K   Jumper John J   de Sanctis Daniele D   Wu Bin B   Jovine Luca L  

Nature structural & molecular biology 20220310 3


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 ne  ...[more]

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