Year: 2021
Type: article
Abstract: In Gram-negative bacteria, the biogenesis of β-barrel outer membrane proteins is mediated by the β-barrel assembly machinery (BAM). The mechanism employed by BAM is complex and so far- incompletely understood. Here, we report the structures of BAM in nanodiscs, prepared using polar lipids and native membranes, where we observe an outward-open state. Mutations in the barrel domain of BamA reveal that plasticity in BAM is essential, particularly along the lateral seam of the barrel domain, which is further supported by molecular dynamics simulations that show conformational dynamics in BAM are modulated by the accessory proteins. We also report the structure of BAM in complex with EspP, which reveals an early folding intermediate where EspP threads from the underside of BAM and incorporates into the barrel domain of BamA, supporting a hybrid-barrel budding mechanism in which the substrate is folded into the membrane sequentially rather than as a single unit.
Source: Nature Communications
Authors: Runrun Wu, Jeremy W. Bakelar, Karl Lundquist, Zijian Zhang, Katie M. Kuo, David Ryoo, Yui Tik Pang, Chen Sun, Tommi White, Thomas Klose, Wen Jiang, James C. Gumbart, Nicholas Noinaj
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: National Science Foundation, U.S. Department of Health and Human Services, Georgia Institute of Technology, Indiana Clinical and Translational Sciences Institute, University of Missouri, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: G1000919138, G1105213051, G1742171491, Mechanistic insight into the role of the BAM complex in E. coli, G2019679569, G2206590661, G3226045097, Dynamic characterization of outer-membrane-protein biogenesis by the BAM and TAM complexes, XSEDE 2.0: Integrating, Enabling and Enhancing National Cyberinfrastructure with Expanding Community Involvement, Unraveling the mechanism by which the BAM complex mediates OMP biogenesis, Structural Characterization of the TOC Protein Translocon Machinery, Midwest Consortium for High Resolution Cryoelectron Microscopy, G7405664548, Neisseria gonorrhoeae metal transporters that subvert nutritional immunity
OpenAlex ID: W4200411548