Authors

Gino Cingolani, Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, PA 19107, United States; Institute of Biomembranes and Bioenergetics, National Research Council, Via Amendola 165/A, Bari, 70126, ItalyFollow
Michael McCauley, Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA 19107, United States; Janssen Research and Development, Spring House, PA 19477, United States
Anna Lobley, Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA 19107, United States
Alexander J Bryer, The University of Delaware, Department of Chemistry and Biochemistry, Newark, DE 19716, United States
Jordan Wesolowski, Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA 19107, United StatesFollow
Deanna L Greco, The University of Delaware, Department of Chemistry and Biochemistry, Newark, DE 19716, United States
Ravi K Lokareddy, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, United StatesFollow
Erik Ronzone, Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA 19107, United States; VUE Health, Boston, MA 02110, United States
Juan R Perilla, The University of Delaware, Department of Chemistry and Biochemistry, Newark, DE 19716, United States
Fabienne Paumet, Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA 19107, United StatesFollow

Document Type

Article

Publication Date

6-21-2019

Comments

This article has been peer reviewed. It was published in: Nature Communications.

2019 Jun 21;10(1):2747.

The published version is available at DOI: 10.1038/s41467-019-10806-9

Copyright © 2019, 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/.

Abstract

Many intracellular bacteria, including Chlamydia, establish a parasitic membrane-bound organelle inside the host cell that is essential for the bacteria's survival. Chlamydia trachomatis forms inclusions that are decorated with poorly characterized membrane proteins known as Incs. The prototypical Inc, called IncA, enhances Chlamydia pathogenicity by promoting the homotypic fusion of inclusions and shares structural and functional similarity to eukaryotic SNAREs. Here, we present the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion during infection.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

31227715

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