A metabolite binding protein moonlights as a bile-responsive chaperone
METADATA ONLY
Loading...
Author / Producer
Date
2020-10-15
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
METADATA ONLY
Data
Rights / License
Abstract
Bile salts are secreted into the gastrointestinal tract to aid in the absorption of lipids. In addition, bile salts show potent antimicrobial activity in part by mediating bacterial protein unfolding and aggregation. Here, using a protein folding sensor, we made the surprising discovery that the Escherichia coli periplasmic glycerol‐3‐phosphate (G3P)‐binding protein UgpB can serve, in the absence of its substrate, as a potent molecular chaperone that exhibits anti‐aggregation activity against bile salt‐induced protein aggregation. The substrate G3P, which is known to accumulate in the later compartments of the digestive system, triggers a functional switch between UgpB's activity as a molecular chaperone and its activity as a G3P transporter. A UgpB mutant unable to bind G3P is constitutively active as a chaperone, and its crystal structure shows that it contains a deep surface groove absent in the G3P‐bound wild‐type UgpB. Our work illustrates how evolution may be able to convert threats into signals that first activate and then inactivate a chaperone at the protein level in a manner that bypasses the need for ATP.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
39 (20)
Pages / Article No.
Publisher
EMBO Press
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
chaperone; protein folding
Organisational unit
03412 - Glockshuber, Rudolf (emeritus) / Glockshuber, Rudolf (emeritus)
Notes
Funding
176403 - Mechanism of assembly and receptor binding of adhesive pili from pathogenic bacteria (SNF)
156304 - Functional significance of the dynamics of receptor binding and the alternative folding possibilities of pilus subunits in urinary tract infections caused by pathogenic Escherichia coli strains (SNF)
156304 - Functional significance of the dynamics of receptor binding and the alternative folding possibilities of pilus subunits in urinary tract infections caused by pathogenic Escherichia coli strains (SNF)