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

Autor: Alena Stsiapanava, Chenrui Xu, Shunsuke Nishio, Ling Han, Nao Yamakawa, Marta Carroni, Kathryn Tunyasuvunakool, John Jumper, Daniele de Sanctis, Bin Wu, Luca Jovine
Přispěvatelé: School of Biological Sciences, NTU Institute of Structural Biology
Jazyk: angličtina
Rok vydání: 2022
Předmět:
ISSN: 2016-0399
Popis: 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. Ministry of Health (MOH) National Medical Research Council (NMRC) Published version This work was supported by the Swedish Research Council (project grants 2016-03999 and 2020-04936 to L.J.), the Karolinska Institutet Research Foundation (grant 2016fobi50035 to L.J.), the Knut and Alice Wallenberg Foundation (project grant 2018.0042 to L.J.) and the Ministry of Health, Singapore, NMRC grant (MOH-000382-00 to B.W.). Open access funding provided by Karolinska Institute.
Databáze: OpenAIRE