title: Structural basis of the proteolytic and chaperone activity of Chlamydia trachomatis CT441.
abstract: Chlamydia trachomatis is the most prevalent cause of preventable blindness worldwide and a major reason for infectious infertility in females. Several bacterial factors have been implicated in the pathogenesis of C. trachomatis. Combining structural and mutational analysis, we have shown that the proteolytic function of CT441 depends on a conserved Ser/Lys/Gln catalytic triad and a functional substrate-binding site within a flexible PDZ (postsynaptic density of 95 kDa, discs large, and zonula occludens) domain. Previously, it has been suggested that CT441 is involved in modulating estrogen signaling responses of the host cell. Our results show that although in vitro CT441 exhibits proteolytic activity against SRAP1, a coactivator of estrogen receptor α, CT441-mediated SRAP1 degradation is not observed during the intracellular developmental cycle before host cells are lysed and infectious chlamydiae are released. Most compellingly, we have newly identified a chaperone activity of CT441, indicating a role of CT441 in prokaryotic protein quality control processes.
authors.affiliation: Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Kohlmann
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany German Center for Infection Research (DZIF), partner site Lübeck, Lübeck, Germany.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shima
authors.affiliation: Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany German Center for Infection Research (DZIF), partner site Lübeck, Lübeck, Germany Laboratory for Structural Biology of Infection and Inflammation, Hamburg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Hilgenfeld
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany German Center for Infection Research (DZIF), partner site Lübeck, Lübeck, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Solbach
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany German Center for Infection Research (DZIF), partner site Lübeck, Lübeck, Germany Medical Clinic III, University Clinic of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
authors.affiliation: Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany hansen@biochem.uni-luebeck.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Hansen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002692:Chlamydia trachomatis / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D011994:Recombinant Proteins
chemical_list: D001426:Bacterial Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins