Hsp110 nucleotide exchange factors may amplify Hsp70-disaggregation by enhanced entropic pulling

Area of Science:

• Molecular biology
• Protein folding
• Chaperone proteins

Background:

• Hsp70 chaperones utilize ATP hydrolysis to unfold proteins and disaggregate protein structures.
• Hsp70 function requires interaction with J-domain proteins (JDPs), substrates, and nucleotide exchange factors (NEFs).
• In eukaryotes, Hsp110s replaced bacterial GrpE as NEFs, despite belonging to the Hsp70 superfamily, posing an evolutionary question.

Purpose of the Study:

• To investigate the evolutionary origins and mechanism of Hsp110 as a NEF.
• To determine if Hsp110 evolved novel properties or repurposed existing Hsp70 features.

Main Methods:

• Utilized wild-type Sse1 (yeast Hsp110) and rationally designed mutants.
• Conducted experiments to analyze Hsp110's interaction with Hsp70 and its NEF activity.

Main Results:

• Hsp110 appears to repurpose existing Hsp70 features rather than acquiring entirely new molecular properties.
• Hsp110 functions as a NEF and enhances the unfolding and disaggregating activity of Hsp70.
• Hsp110 increases Hsp70's effective volume, boosting entropic pulling forces.

Conclusions:

• Hsp110 evolved from Hsp70s by repurposing ancestral features.
• Hsp110 acts as a NEF and potentiates Hsp70's chaperone activity through a novel mechanism.
• This study elucidates the evolution and function of Hsp110 in protein homeostasis.