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Cryo-EM structures reveal multiple stages of bacterial outer membrane protein folding

2022; Cell Press; Volume: 185; Issue: 7 Linguagem: Inglês

10.1016/j.cell.2022.02.016

1097-4172

Matthew Thomas Doyle, John R. Jimah, Tyrone Dowdy, Shannon I. Ohlemacher, Mioara Larion, Jenny E. Hinshaw, Harris D. Bernstein,

Escherichia coli research studies

Transmembrane β barrel proteins are folded into the outer membrane (OM) of Gram-negative bacteria by the β barrel assembly machinery (BAM) via a poorly understood process that occurs without known external energy sources. Here, we used single-particle cryo-EM to visualize the folding dynamics of a model β barrel protein (EspP) by BAM. We found that BAM binds the highly conserved "β signal" motif of EspP to correctly orient β strands in the OM during folding. We also found that the folding of EspP proceeds via "hybrid-barrel" intermediates in which membrane integrated β sheets are attached to the essential BAM subunit, BamA. The structures show an unprecedented deflection of the membrane surrounding the EspP intermediates and suggest that β sheets progressively fold toward BamA to form a β barrel. Along with in vivo experiments that tracked β barrel folding while the OM tension was modified, our results support a model in which BAM harnesses OM elasticity to accelerate β barrel folding.