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.

Details

Title
Structural basis for the homotypic fusion of chlamydial inclusions by the SNARE-like protein IncA
Author
Cingolani, Gino 1 ; McCauley, Michael 2   VIAFID ORCID Logo  ; Lobley, Anna 3 ; Bryer, Alexander J 4 ; Wesolowski, Jordan 3 ; Greco, Deanna L 4 ; Lokareddy, Ravi K 5 ; Ronzone, Erik 6 ; Perilla, Juan R 4   VIAFID ORCID Logo  ; Paumet, Fabienne 3 

1  Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, PA, USA; Institute of Biomembranes and Bioenergetics, National Research Council, Bari, Italy 
2  Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA, USA; Janssen Research and Development, Spring House, PA, USA 
3  Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA, USA 
4  The University of Delaware, Department of Chemistry and Biochemistry, Newark, DE, USA 
5  Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, PA, USA 
6  Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA, USA; VUE Health, Boston, MA, USA 
Pages
1-12
Publication year
2019
Publication date
Jun 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-10806-9
ProQuest document ID
2244645794
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.