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Distinct isoforms of the cofactor BAG-1 differentially affect Hsc70 chaperone function.
1Max Planck Institute for Biochemistry, Department of Molecular Cell Biology, D-82152 Martinsried, Germany.
The Journal of Biological Chemistry
|May 16, 2000
Summary
The anti-apoptotic protein BAG-1 has distinct isoforms that oppositely regulate the Hsc70 chaperone. BAG-1S stimulates Hsc70 activity, while BAG-1M inhibits it, influencing protein folding outcomes.
Area of Science:
- Molecular biology
- Cellular biology
- Protein biochemistry
Background:
- Hsc70 chaperone activity is modulated by cofactors in the cytosol and nucleus.
- BAG-1 is an anti-apoptotic protein functioning as an Hsc70 cofactor.
- BAG-1 exists in multiple isoforms differing in their amino termini.
Purpose of the Study:
- To investigate differential Hsc70-regulating activities among BAG-1 isoforms.
- To compare the effects of BAG-1M and BAG-1S on Hsc70-assisted protein folding.
Main Methods:
- Comparative analysis of BAG-1M and BAG-1S isoforms in chaperone-assisted folding reactions.
- Assessment of Hsc70 ATPase activity modulation by BAG-1 isoforms.
- Investigation of Hsp40-dependent mechanisms.
Main Results:
- BAG-1M inhibited Hsc70-mediated refolding of nonnative polypeptides.
- BAG-1S isoform stimulated Hsc70 chaperone activity.
- Both isoforms accelerated ADP-ATP exchange, stimulating Hsc70 ATPase activity in an Hsp40-dependent manner.
Conclusions:
- Distinct BAG-1 isoform amino termini dictate Hsc70-mediated folding outcomes.
- Isoform-specific substrate interactions likely mediate differential effects on Hsc70 function.
- Differential cofactor isoform substrate binding influences Hsc70 chaperone function beyond ATPase cycle modulation.