Dynamic interplay between the periplasmic chaperone SurA and the BAM complex in outer membrane protein folding.
Bob SchiffrinJonathan M MachinTheodoros K KaramanosAnastasia ZhuravlevaDavid J BrockwellSheena E RadfordAntonio N CalabresePublished in: Communications biology (2022)
Correct folding of outer membrane proteins (OMPs) into the outer membrane of Gram-negative bacteria depends on delivery of unfolded OMPs to the β-barrel assembly machinery (BAM). How unfolded substrates are presented to BAM remains elusive, but the major OMP chaperone SurA is proposed to play a key role. Here, we have used hydrogen deuterium exchange mass spectrometry (HDX-MS), crosslinking, in vitro folding and binding assays and computational modelling to show that the core domain of SurA and one of its two PPIase domains are key to the SurA-BAM interaction and are required for maximal catalysis of OMP folding. We reveal that binding causes changes in BAM and SurA conformation and/or dynamics distal to the sites of binding, including at the BamA β1-β16 seam. We propose a model for OMP biogenesis in which SurA plays a crucial role in OMP delivery and primes BAM to accept substrates for folding.
Keyphrases
- single molecule
- molecular dynamics simulations
- mass spectrometry
- endoplasmic reticulum
- endoplasmic reticulum stress
- heat shock protein
- binding protein
- dna binding
- multiple sclerosis
- liquid chromatography
- heat shock
- high resolution
- blood pressure
- genome wide
- oxidative stress
- gas chromatography
- resistance training
- electron transfer