Inter-domain dynamics in the chaperone SurA and multi-site binding to its unfolded outer membrane protein clients
Antonio N Calabrese,
Theodoros K Karamanos,
Julia R Humes,
Jim E. Horne,
Andrew J Wilson,
Antreas C Kalli,
Alison E Ashcroft,
David. J. Brockwell,
Sheena E. Radford
Posted 20 Dec 2019
bioRxiv DOI: 10.1101/2019.12.19.882696 (published DOI: 10.1038/s41467-020-15702-1)
Posted 20 Dec 2019
The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but how it binds its OMP clients and the mechanism(s) of its chaperone action remain unclear. Here, we have used chemical cross-linking, hydrogen-deuterium exchange, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and to interrogate the role of conformational dynamics of the chaperone's domains in OMP recognition. We demonstrate that SurA samples a broad array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested by its crystal structure. Multiple binding sites for OMPs are located primarily in the core domain, with binding of the unfolded OMP resulting in conformational changes between the core/P1 domains. Together, the results portray a model in which unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between its domains assisting OMP recognition, binding and release.
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