title: Large nucleotide-dependent movement of the N-terminal domain of the ClpX chaperone.
abstract: The ClpXP ATPase-protease complex is a major component of the protein quality control machinery in the cell. A ClpX subunit consists of an N-terminal zinc binding domain (ZBD) and a C-terminal AAA+ domain. ClpX oligomerizes into a hexamer with the AAA+ domains forming the base of the hexamer and the ZBDs extending out of the base. Here, we report that ClpX switches between a capture and a feeding conformation. ZBDs in ClpX undergo large nucleotide-dependent block movement towards ClpP and into the AAA+ ring. This motion is modulated by the ClpX cofactor, SspB. Evidence for this movement was initially obtained by the surprising observation that an N-terminal extension on ClpX is clipped by bound ClpP in functional ClpXP complexes. Protease-protection, crosslinking, and light scattering experiments further support these findings.
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Thibault
authors.forename: Yulia
authors.initials: Y
authors.lastname: Tsitrin
authors.forename: Toni
authors.initials: T
authors.lastname: Davidson
authors.forename: Anna
authors.initials: A
authors.lastname: Gribun
authors.forename: Walid A
authors.initials: WA
authors.lastname: Houry
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism; D001693:Biological Transport, Active / Q000502:physiology; D049071:Endopeptidase Clp / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D004926:Escherichia coli / Q000201:enzymology / Q000502:physiology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D009711:Nucleotides / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D009711:Nucleotides; D010446:Peptide Fragments; D012697:Serine Endopeptidases; C483572:ClpP protease, E coli; C501427:ClpP protein, Streptococcus pneumoniae; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases; C088072:ClpX protein, E coli; D000074183:ATPases Associated with Diverse Cellular Activities