title: Unique residues involved in activation of the multitasking protease/chaperone HtrA from Chlamydia trachomatis.
abstract: DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia. w.huston@qut.edu.au
authors.forename: Wilhelmina M
authors.initials: WM
authors.lastname: Huston
authors.forename: Joel D A
authors.initials: JD
authors.lastname: Tyndall
authors.forename: William B
authors.initials: WB
authors.lastname: Lott
authors.forename: Scott H
authors.initials: SH
authors.lastname: Stansfield
authors.forename: Peter
authors.initials: P
authors.lastname: Timms
mesh_terms: D000495:Allosteric Site; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry; D002692:Chlamydia trachomatis / Q000201:enzymology*; D004926:Escherichia coli / Q000235:genetics; D006360:Heat-Shock Proteins / Q000737:chemistry*; D007700:Kinetics; D018832:Molecular Chaperones / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D033903:Periplasmic Proteins / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D040901:Proteomics / Q000379:methods; D012697:Serine Endopeptidases / Q000737:chemistry*; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D001425:Bacterial Outer Membrane Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010455:Peptides; D033903:Periplasmic Proteins; C078167:OMPA outer membrane proteins; C061682:DegP protease; D012697:Serine Endopeptidases