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Hsp90-Tau Complex Reveals Molecular Basis for Specificity in Chaperone Action
- Source :
- Cell, Cell, 156(5), 963-974. Cell Press, Europe PubMed Central, Cell 156(5), 963-974 (2014). doi:10.1016/j.cell.2014.01.037, Cell 156, 963-974 (2014), Cell, 156(5), 963. Cell Press
- Publication Year :
- 2014
-
Abstract
- Protein folding in the cell relies on the orchestrated action of conserved families of molecular chaperones, the Hsp70 and Hsp90 systems. Hsp70 acts early and Hsp90 late in the folding path, yet the molecular basis of this timing is enigmatic, mainly because the substrate specificity of Hsp90 is poorly understood. Here, we obtained a structural model of Hsp90 in complex with its natural disease-associated substrate, the intrinsically disordered Tau protein. Hsp90 binds to a broad region in Tau that includes the aggregation-pronerepeats. Complementarily, a 106-Å-long substrate-binding interface in Hsp90 enables many low-affinity contacts. This allows recognition of scattered hydrophobic residues in late folding intermediates that remain after early burial of the Hsp70 sites. Our model resolves the paradox of how Hsp90 specifically selects for late folding intermediates but also for some intrinsically disordered proteins-through the eyes of Hsp90 they look the same.
- Subjects :
- Models, Molecular
Protein Folding
Plasma protein binding
protein binding
Protein aggregation
0302 clinical medicine
Protein structure
X-Ray Diffraction
protein folding
binding affinity
polycyclic compounds
drug therapy [Alzheimer Disease]
Peptide sequence
0303 health sciences
metabolism [HSP90 Heat-Shock Proteins]
article
protein domain
protein function
structure analysis
Biochemistry
Protein folding
microtubule
chemistry [HSP90 Heat-Shock Proteins]
Protein domain
adenosine triphosphate
Molecular Sequence Data
tau Proteins
Biology
General Biochemistry, Genetics and Molecular Biology
tau protein
Article
protein aggregation
03 medical and health sciences
Alzheimer Disease
complex formation
Scattering, Small Angle
Humans
controlled study
ddc:610
human
Amino Acid Sequence
HSP90 Heat-Shock Proteins
Binding site
heat shock protein 90
protein structure
030304 developmental biology
hydrophobicity
binding site
Biochemistry, Genetics and Molecular Biology(all)
chemistry [tau Proteins]
intrinsically disordered protein
metabolism [tau Proteins]
molecular dynamics
Chaperone (protein)
Biophysics
biology.protein
amino terminal sequence
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00928674
- Volume :
- 156
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....c71a1240dfd843ee70b399e9af2ba17a