title: An α-helical core encodes the dual functions of the chlamydial protein IncA.
abstract: Chlamydia is an intracellular bacterium that establishes residence within parasitophorous compartments (inclusions) inside host cells. Chlamydial inclusions are uncoupled from the endolysosomal pathway and undergo fusion with cellular organelles and with each other. To do so, Chlamydia expresses proteins on the surface of the inclusion using a Type III secretion system. These proteins, termed Incs, are located at the interface between host and pathogen and carry out the functions necessary for Chlamydia survival. Among these Incs, IncA plays a critical role in both protecting the inclusion from lysosomal fusion and inducing the homotypic fusion of inclusions. Within IncA are two regions homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) domains referred to as SNARE-like domain 1 (SLD1) and SNARE-like domain 2 (SLD2). Using a multidisciplinary approach, we have discovered the functional core of IncA that retains the ability to both inhibit SNARE-mediated fusion and promote the homotypic fusion of Chlamydia inclusions. Circular dichroism and analytical ultracentrifugation experiments show that this core region is composed almost entirely of α-helices and assembles into stable homodimers in solution. Altogether, we propose that both IncA functions are encoded in a structured core domain that encompasses SLD1 and part of SLD2.
authors.affiliation: From the Departments of Microbiology and Immunology and.
authors.forename: Erik
authors.initials: E
authors.lastname: Ronzone
authors.affiliation: From the Departments of Microbiology and Immunology and.
authors.forename: Jordan
authors.initials: J
authors.lastname: Wesolowski
authors.affiliation: the Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Bauler
authors.affiliation: Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 and.
authors.forename: Anshul
authors.initials: A
authors.lastname: Bhardwaj
authors.affiliation: the Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840.
authors.forename: Ted
authors.initials: T
authors.lastname: Hackstadt
authors.affiliation: From the Departments of Microbiology and Immunology and fabienne.paumet@jefferson.edu.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Paumet
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002692:Chlamydia trachomatis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002942:Circular Dichroism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; C460868:IncA protein, Chlamydia trachomatis; D008565:Membrane Proteins
keywords: Bacteria; Chlamydia trachomatis; Infectious Disease; Intracellular Trafficking; SNARE Proteins