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Determinants of structural and functional plasticity of a widely conserved protease chaperone complex.
- Source :
-
Nature structural & molecular biology [Nat Struct Mol Biol] 2010 Jul; Vol. 17 (7), pp. 837-43. Date of Electronic Publication: 2010 Jun 27. - Publication Year :
- 2010
-
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.
- Subjects :
- Amino Acid Sequence
Bacteria genetics
Bacterial Proteins genetics
Catalytic Domain
Heat-Shock Proteins genetics
Models, Molecular
PDZ Domains
Peptides chemistry
Peptides metabolism
Periplasmic Proteins genetics
Point Mutation
Protein Binding
Protein Folding
Protein Multimerization
Serine Endopeptidases genetics
Bacteria metabolism
Bacterial Proteins chemistry
Bacterial Proteins metabolism
Heat-Shock Proteins chemistry
Heat-Shock Proteins metabolism
Periplasmic Proteins chemistry
Periplasmic Proteins metabolism
Serine Endopeptidases chemistry
Serine Endopeptidases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1545-9985
- Volume :
- 17
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Nature structural & molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 20581826
- Full Text :
- https://doi.org/10.1038/nsmb.1839