@article{202561,
  keywords = {Escherichia coli, Escherichia coli Proteins, Protein Folding, Cryoelectron Microscopy, Bacterial Outer Membrane Proteins},
  author = {Matthew Thomas* Doyle and John Jimah and Tyrone Dowdy and Shannon Ohlemacher and Mioara Larion and Jenny Hinshaw and Harris Bernstein},
  title = {Cryo-EM structures reveal multiple stages of bacterial outer membrane protein folding},
  abstract = {<p>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\&nbsp;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.</p>
},
  year = {2022},
  journal = {Cell},
  volume = {185},
  pages = {1143-1156.e13 (* co-first authors)},
  month = {03/2022},
  issn = {1097-4172},
  doi = {10.1016/j.cell.2022.02.016},
  language = {eng},
}