title: Determinants of structural and functional plasticity of a widely conserved protease chaperone complex.
abstract: Channeling of misfolded proteins into repair, assembly or degradation pathways is often mediated by complex and multifunctional cellular factors. Despite detailed structural information, the underlying regulatory mechanisms governing these factors are not well understood. The extracytoplasmic heat-shock factor DegP (HtrA) is a well-suited model for addressing mechanistic issues, as it is regulated by the common mechanisms of allostery and activation by oligomerization. Site-directed mutagenesis combined with refolding and oligomerization studies of chemically denatured DegP revealed how substrates trigger the conversion of the resting conformation into the active conformation. Binding of specific peptides to PDZ domain-1 causes a local rearrangement that is allosterically transmitted to the substrate-binding pocket of the protease domain. This activated state readily assembles into larger oligomeric particles, thus stabilizing the catalytically active form and providing a degradation cavity for protein substrates. The implications of these data for the mechanism of protein quality control are discussed.
authors.affiliation: Centre for Medical Biotechnology, FB Biology and Geography, University Duisburg-Essen, Essen, Germany.
authors.forename: Melisa
authors.initials: M
authors.lastname: Merdanovic
authors.forename: Nicolette
authors.initials: N
authors.lastname: Mamant
authors.forename: Michael
authors.initials: M
authors.lastname: Meltzer
authors.forename: Simon
authors.initials: S
authors.lastname: Poepsel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Auckenthaler
authors.forename: Rie
authors.initials: R
authors.lastname: Melgaard
authors.forename: Patrick
authors.initials: P
authors.lastname: Hauske
authors.forename: Luitgard
authors.initials: L
authors.lastname: Nagel-Steger
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Clarke
authors.forename: Markus
authors.initials: M
authors.lastname: Kaiser
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrmann
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D054731:PDZ Domains; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D033903:Periplasmic Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D010455:Peptides; D033903:Periplasmic Proteins; C061682:DegP protease; D012697:Serine Endopeptidases