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Nat Commun. 2019 Jun 21;10(1):2747. doi: 10.1038/s41467-019-10806-9.

Structural basis for the homotypic fusion of chlamydial inclusions by the SNARE-like protein IncA.

Author information

1
Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, PA, 19107, USA. gino.cingolani@jefferson.edu.
2
Institute of Biomembranes and Bioenergetics, National Research Council, Via Amendola 165/A, 70126, Bari, Italy. gino.cingolani@jefferson.edu.
3
Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA, 19107, USA.
4
Janssen Research and Development, Spring House, PA, 19477, USA.
5
The University of Delaware, Department of Chemistry and Biochemistry, Newark, DE, 19716, USA.
6
Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, PA, 19107, USA.
7
VUE Health, Boston, MA, 02110, USA.
8
Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA, 19107, USA. fabienne.paumet@jefferson.edu.

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.

PMID:
31227715
PMCID:
PMC6588587
DOI:
10.1038/s41467-019-10806-9
[Indexed for MEDLINE]
Free PMC Article

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