title: Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ.
abstract: The HtrA protein family combines chaperone and protease activities and is essential for protein quality control in many organisms. Whereas the mechanisms underlying the proteolytic function of HtrA proteins are well characterized, their chaperone activity remains poorly understood. Here we describe cryo-EM structures of Escherichia coli DegQ in its 12- and 24-mer states in complex with model substrates, providing a structural model of HtrA chaperone action. Up to six lysozyme substrates bind inside the DegQ 12-mer cage and are visualized in a close-to-native state. An asymmetric reconstruction reveals the binding of a well-ordered lysozyme to four DegQ protomers. DegQ PDZ domains are located adjacent to substrate density and their presence is required for chaperone activity. The substrate-interacting regions appear conserved in 12- and 24-mer cages, suggesting a common mechanism of chaperone function.
authors.affiliation: Institute of Structural and Molecular Biology, Crystallography, Birkbeck College, London, UK.
authors.forename: Hélène
authors.initials: H
authors.lastname: Malet
authors.forename: Flavia
authors.initials: F
authors.lastname: Canellas
authors.forename: Justyna
authors.initials: J
authors.lastname: Sawa
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Thalassinos
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrmann
authors.forename: Tim
authors.initials: T
authors.lastname: Clausen
authors.forename: Helen R
authors.initials: HR
authors.lastname: Saibil
mesh_terms: D020285:Cryoelectron Microscopy; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D009113:Muramidase; C098059:DegQ protein, E coli; D012697:Serine Endopeptidases