Nejvíce citovaný článek - PubMed ID 32358557
Inter-domain dynamics in the chaperone SurA and multi-site binding to its outer membrane protein clients
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.
- MeSH
- ABC transportéry metabolismus chemie genetika MeSH
- adenosintrifosfát metabolismus MeSH
- Escherichia coli * metabolismus genetika MeSH
- molekulární chaperony * metabolismus MeSH
- molekulární modely MeSH
- peptidylprolylisomerasa * metabolismus genetika MeSH
- proteinové domény MeSH
- proteiny vnější bakteriální membrány metabolismus genetika chemie MeSH
- proteiny z Escherichia coli * metabolismus genetika chemie MeSH
- rezonanční přenos fluorescenční energie MeSH
- sbalování proteinů MeSH
- transportní proteiny * metabolismus MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportéry MeSH
- adenosintrifosfát MeSH
- molekulární chaperony * MeSH
- peptidylprolylisomerasa * MeSH
- proteiny vnější bakteriální membrány MeSH
- proteiny z Escherichia coli * MeSH
- SurA protein, E coli MeSH Prohlížeč
- transportní proteiny * MeSH