A metabolite binding protein moonlights as a bile-responsive chaperone

Area of Science:

• Biochemistry
• Molecular Biology
• Microbiology

Background:

• Bile salts aid lipid absorption and possess antimicrobial properties by inducing protein unfolding and aggregation.
• The Escherichia coli periplasmic glycerol-3-phosphate (G3P)-binding protein UgpB is involved in nutrient transport.

Purpose of the Study:

• To investigate the potential chaperone activity of UgpB in the context of bile salt-induced protein aggregation.
• To elucidate the mechanism by which G3P influences UgpB's function.

Main Methods:

• Utilized a protein folding sensor to monitor protein aggregation.
• Characterized UgpB's chaperone activity in the presence and absence of its substrate G3P.
• Determined the crystal structure of a G3P-binding deficient UgpB mutant.

Main Results:

• Escherichia coli UgpB functions as a potent molecular chaperone, inhibiting bile salt-induced protein aggregation when its substrate (G3P) is absent.
• G3P binding induces a functional switch, converting UgpB from a chaperone to a G3P transporter.
• A UgpB mutant lacking G3P-binding capability exhibits constitutive chaperone activity and possesses a distinct surface groove compared to wild-type UgpB.

Conclusions:

• UgpB's chaperone activity is regulated by its substrate G3P, demonstrating a novel mechanism for controlling protein stability in response to environmental cues.
• Evolution has repurposed UgpB to manage threats like bile salts by modulating chaperone activity, bypassing ATP-dependent pathways.