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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / ultrastructure*
  • Chlamydia Infections / microbiology*
  • Chlamydia trachomatis / genetics
  • Chlamydia trachomatis / metabolism
  • Chlamydia trachomatis / pathogenicity*
  • Crystallography, X-Ray
  • Gene Knockout Techniques
  • HeLa Cells
  • Humans
  • Inclusion Bodies / microbiology*
  • Membrane Fusion*
  • Molecular Dynamics Simulation
  • Mutagenesis
  • Protein Conformation, alpha-Helical
  • Protein Domains / genetics
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure
  • SNARE Proteins / chemistry


  • Bacterial Proteins
  • Recombinant Proteins
  • SNARE Proteins