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

Author

Listed:
  • Gino Cingolani

    (Thomas Jefferson University, Department of Biochemistry and Molecular Biology
    Institute of Biomembranes and Bioenergetics, National Research Council)

  • Michael McCauley

    (Thomas Jefferson University, Department of Microbiology and Immunology
    Janssen Research and Development)

  • Anna Lobley

    (Thomas Jefferson University, Department of Microbiology and Immunology)

  • Alexander J. Bryer

    (The University of Delaware, Department of Chemistry and Biochemistry)

  • Jordan Wesolowski

    (Thomas Jefferson University, Department of Microbiology and Immunology)

  • Deanna L. Greco

    (The University of Delaware, Department of Chemistry and Biochemistry)

  • Ravi K. Lokareddy

    (Thomas Jefferson University, Department of Biochemistry and Molecular Biology)

  • Erik Ronzone

    (Thomas Jefferson University, Department of Microbiology and Immunology
    VUE Health)

  • Juan R. Perilla

    (The University of Delaware, Department of Chemistry and Biochemistry)

  • Fabienne Paumet

    (Thomas Jefferson University, Department of Microbiology and Immunology)

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.

Suggested Citation

  • Gino Cingolani & Michael McCauley & Anna Lobley & Alexander J. Bryer & Jordan Wesolowski & Deanna L. Greco & Ravi K. Lokareddy & Erik Ronzone & Juan R. Perilla & Fabienne Paumet, 2019. "Structural basis for the homotypic fusion of chlamydial inclusions by the SNARE-like protein IncA," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10806-9
    DOI: 10.1038/s41467-019-10806-9
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    Cited by:

    1. Christine Linton & Jordan Wesolowski & Anna Lobley & Toshiyuki Yamaji & Kentaro Hanada & Fabienne Paumet, 2024. "Specialized contact sites regulate the fusion of chlamydial inclusion membranes," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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