Regulation of chaperone function by coupled folding and oligomerization

Mas, Guillaume and Burmann, Björn M. and Sharpe, Timothy and Claudi, Beatrice and Bumann, Dirk and Hiller, Sebastian. (2020) Regulation of chaperone function by coupled folding and oligomerization. Science advances, 6 (43). eabc5822.

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The homotrimeric molecular chaperone Skp of Gram-negative bacteria facilitates the transport of outer membrane proteins across the periplasm. It has been unclear how its activity is modulated during its functional cycle. Here, we report an atomic-resolution characterization of the; Escherichia coli; Skp monomer-trimer transition. We find that the monomeric state of Skp is intrinsically disordered and that formation of the oligomerization interface initiates folding of the α-helical coiled-coil arms via a unique "stapling" mechanism, resulting in the formation of active trimeric Skp. Native client proteins contact all three Skp subunits simultaneously, and accordingly, their binding shifts the Skp population toward the active trimer. This activation mechanism is shown to be essential for; Salmonella; fitness in a mouse infection model. The coupled mechanism is a unique example of how an ATP-independent chaperone can modulate its activity as a function of the presence of client proteins.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller)
05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Biophysics Facility (Sharpe)
UniBasel Contributors:Bumann, Dirk and Hiller, Sebastian and Sharpe, Timothy
Item Type:Article, refereed
Article Subtype:Research Article
Publisher: American Association for the Advancement of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Jul 2021 03:10
Deposited On:30 Dec 2020 10:34

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