The extracellular juncture domains in the intimin passenger adopt a constitutively extended conformation inducing restraints to its sphere of action

Weikum, J., Kulakova, A., Tesei, G., Yoshimoto, S., Vejby Jaegerum, L., Schuetz, M., Hori, K., Skepoe, M., Harris, P., Leo, J.C. ORCID: 0000-0002-7066-7527 and Morth, J.P., 2020. The extracellular juncture domains in the intimin passenger adopt a constitutively extended conformation inducing restraints to its sphere of action. Scientific Reports, 10: 21249.

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Abstract

Enterohemorrhagic and enteropathogenic Escherichia coli are among the most important food-borne pathogens, posing a global health threat of bloody diarrhea and hemolytic uremic syndrome outbreaks. The virulence factor intimin is essential for attachment and internalization into the host cells of a broad range of effacing pathogens. Intimin is translocated to the bacterial outer membrane and includes an extracellular passenger, which consists of four bacterial immunoglobulin (Big) like domains, D00-D2, extending into the fifth subdomain, a C-terminal lectin domain (D3) that binds to the Tir-receptor on the host cell. Here, we present the crystal structures of D00-D0 at 1.5 Å and D0-D1 at 1.8 Å resolution that confirm that the passenger of intimin has five distinct domains. SAXS and MD simulations show that the connector region between D00-D0 has a higher degree of rigidity and D00 likely functions as a juncture domain at the outer membrane-extracellular medium interface. We describe D00 as a Big domain with a specific topology found in the equivalent position in a broad range of other inverse autotransporters, including the structurally uncharacterized D0 domain in invasin. The accumulated data allows us to model the complete passenger of intimin and propose functionality to the Big domains, D00-D0-D1, extending directly from the membrane.

Item Type: Journal article
Publication Title: Scientific Reports
Creators: Weikum, J., Kulakova, A., Tesei, G., Yoshimoto, S., Vejby Jaegerum, L., Schuetz, M., Hori, K., Skepoe, M., Harris, P., Leo, J.C. and Morth, J.P.
Publisher: Nature Research (part of Springer Nature)
Date: 4 December 2020
Volume: 10
Identifiers:
NumberType
10.1038/s41598-020-77706-7DOI
1386304Other
Rights: © The Author(s) 2020. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 08 Dec 2020 09:41
Last Modified: 08 Dec 2020 09:41
URI: http://irep.ntu.ac.uk/id/eprint/41808

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