Structural basis for the homotypic fusion of chlamydial inclusions by the SNARE-like protein IncA.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31227715.
- Also identified by DOI 10.1038/s41467-019-10806-9 and PMC identifier 6588587.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Bacterial Proteins
- Chlamydia Infections
- Chlamydia trachomatis
- Inclusion Bodies
- Membrane Fusion