Unique structural features of a bacterial autotransporter adhesin suggest mechanisms for interaction with host macromolecules

Paxman, Jason J., Lo, Alvin W., Sullivan, Matthew J. ORCID: https://orcid.org/0000-0003-2276-3132, Panjikar, Santosh, Kuiper, Michael, Whitten, Andrew E., Wang, Geqing, Luan, Chi-Hao, Moriel, Danilo G., Tan, Lendl, Peters, Kate M., Phan, Minh-Duy, Gee, Christine L., Ulett, Glen C., Schembri, Mark A. and Heras, Begoña (2019) Unique structural features of a bacterial autotransporter adhesin suggest mechanisms for interaction with host macromolecules. Nature Communications, 10. ISSN 2041-1723

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Autotransporters are the largest family of outer membrane and secreted proteins in Gram-negative bacteria. Most autotransporters are localised to the bacterial surface where they promote colonisation of host epithelial surfaces. Here we present the crystal structure of UpaB, an autotransporter that is known to contribute to uropathogenic E. coli (UPEC) colonisation of the urinary tract. We provide evidence that UpaB can interact with glycosaminoglycans and host fibronectin. Unique modifications to its core β-helical structure create a groove on one side of the protein for interaction with glycosaminoglycans, while the opposite face can bind fibronectin. Our findings reveal far greater diversity in the autotransporter β-helix than previously thought, and suggest that this domain can interact with host macromolecules. The relevance of these interactions during infection remains unclear.

Item Type: Article
Additional Information: Funding Information: This work was supported by an Australian Research Council (ARC) project grant (DP150102287, DP180102987), a La Trobe University Research Focus Area Understanding Disease Express Grant and a Victorian Life Sciences Computation Initiative grant (LTU0011) on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government, Australia. B.H. is supported by an ARC Future Fellowship (FT130100580) and M.A.S. by an Australian National Health and Medical Research Council Senior Research Fellowship (GNT1106930). We thank Dr. Salvatore Nocadello for getting us in contact with Professor Chi-Hao Luan. We thank Lahiru Katupitiya and Dean Gosling for excellent technical assistance. We acknowledge use of the MX2 and SAXS beamlines at the Australian Synchrotron and the CSIRO Collaborative Crystallisation Centre (www.csiro.au/C3; Melbourne, Australia). Publisher Copyright: © 2019, The Author(s).
Uncontrolled Keywords: chemistry(all),biochemistry, genetics and molecular biology(all),physics and astronomy(all) ,/dk/atira/pure/subjectarea/asjc/1600
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Depositing User: LivePure Connector
Date Deposited: 15 Aug 2022 10:31
Last Modified: 24 Oct 2022 06:49
URI: https://ueaeprints.uea.ac.uk/id/eprint/87243
DOI: 10.1038/s41467-019-09814-6

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