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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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

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spelling	sg-ntu-dr.10356-1629762023-02-28T17:09:52Z Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH Stsiapanava, Alena Xu, Chenrui Nishio, Shunsuke Han, Ling Yamakawa, Nao Carroni, Marta Tunyasuvunakool, Kathryn Jumper, John de Sanctis, Daniele Wu, Bin Jovine, Luca School of Biological Sciences NTU Institute of Structural Biology Science::Biological sciences Cryo-EM Structure Refinement 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. 2022-11-14T05:40:08Z 2022-11-14T05:40:08Z 2022 Journal Article Stsiapanava, A., Xu, C., Nishio, S., Han, L., Yamakawa, N., Carroni, M., Tunyasuvunakool, K., Jumper, J., de Sanctis, D., Wu, B. & Jovine, L. (2022). Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH. Nature Structural & Molecular Biology, 29(3), 190-193. https://dx.doi.org/10.1038/s41594-022-00729-3 1545-9993 https://hdl.handle.net/10356/162976 10.1038/s41594-022-00729-3 35273390 2-s2.0-85126028809 3 29 190 193 en MOH-000382-00 Nature Structural & Molecular Biology © 2022 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. application/pdf
institution	Nanyang Technological University
building	NTU Library
continent	Asia
country	Singapore Singapore
content_provider	NTU Library
collection	DR-NTU
language	English
topic	Science::Biological sciences Cryo-EM Structure Refinement
spellingShingle	Science::Biological sciences Cryo-EM Structure Refinement Stsiapanava, Alena Xu, Chenrui Nishio, Shunsuke Han, Ling Yamakawa, Nao Carroni, Marta Tunyasuvunakool, Kathryn Jumper, John de Sanctis, Daniele Wu, Bin Jovine, Luca Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
description	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.
author2	School of Biological Sciences
author_facet	School of Biological Sciences Stsiapanava, Alena Xu, Chenrui Nishio, Shunsuke Han, Ling Yamakawa, Nao Carroni, Marta Tunyasuvunakool, Kathryn Jumper, John de Sanctis, Daniele Wu, Bin Jovine, Luca
format	Article
author	Stsiapanava, Alena Xu, Chenrui Nishio, Shunsuke Han, Ling Yamakawa, Nao Carroni, Marta Tunyasuvunakool, Kathryn Jumper, John de Sanctis, Daniele Wu, Bin Jovine, Luca
author_sort	Stsiapanava, Alena
title	Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
title_short	Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
title_full	Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
title_fullStr	Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
title_full_unstemmed	Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
title_sort	structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin fimh
publishDate	2022
url	https://hdl.handle.net/10356/162976
_version_	1759855467800035328

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

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