Dual client binding sites in the ATP-independent chaperone SurA

Bob Schiffrin, Joel A. Crossley, Martin Walko, Jonathan M. Machin, G. Nasir Khan, Iain W. Manfield, Andrew J. Wilson, David J. Brockwell, Tomas Fessl, Antonio N. Calabrese, Sheena E. Radford () and Anastasia Zhuravleva ()
Additional contact information
Bob Schiffrin: University of Leeds
Joel A. Crossley: University of Leeds
Martin Walko: University of Leeds
Jonathan M. Machin: University of Leeds
G. Nasir Khan: University of Leeds
Iain W. Manfield: University of Leeds
Andrew J. Wilson: University of Leeds
David J. Brockwell: University of Leeds
Tomas Fessl: Faculty of Science, University of South Bohemia
Antonio N. Calabrese: University of Leeds
Sheena E. Radford: University of Leeds
Anastasia Zhuravleva: University of Leeds

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract The ATP-independent chaperone SurA protects unfolded outer membrane proteins (OMPs) from aggregation in the periplasm of Gram-negative bacteria, and delivers them to the β-barrel assembly machinery (BAM) for folding into the outer membrane (OM). Precisely how SurA recognises and binds its different OMP clients remains unclear. Escherichia coli SurA comprises three domains: a core and two PPIase domains (P1 and P2). Here, by combining methyl-TROSY NMR, single-molecule Förster resonance energy transfer (smFRET), and bioinformatics analyses we show that SurA client binding is mediated by two binding hotspots in the core and P1 domains. These interactions are driven by aromatic-rich motifs in the client proteins, leading to SurA core/P1 domain rearrangements and expansion of clients from collapsed, non-native states. We demonstrate that the core domain is key to OMP expansion by SurA, and uncover a role for SurA PPIase domains in limiting the extent of expansion. The results reveal insights into SurA-OMP recognition and the mechanism of activation for an ATP-independent chaperone, and suggest a route to targeting the functions of a chaperone key to bacterial virulence and OM integrity.

Date: 2024
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DOI: 10.1038/s41467-024-52021-1

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