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Publication Abstract from PubMed

The beta-barrel assembly machinery (BAM complex) is essential for outer membrane protein (OMP) folding in Gram-negative bacteria, and represents a promising antimicrobial target. Several conformational states of BAM have been reported, but all have been obtained under conditions which lack the unique features and complexity of the outer membrane (OM). Here, we use Pulsed Electron-Electron Double Resonance (PELDOR, or DEER) spectroscopy distance measurements to interrogate the conformational ensemble of the BAM complex in E. coli cells. We show that BAM adopts a broad ensemble of conformations in the OM, while in the presence of the antibiotic darobactin B (DAR-B), BAM's conformational equilibrium shifts to a restricted ensemble consistent with the lateral closed state. Our in-cell PELDOR findings are supported by new cryoEM structures of BAM in the presence and absence of DAR-B. This work demonstrates the utility of PELDOR to map conformational changes in BAM within its native cellular environment.

Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex in E. coli Cells.,Haysom SF, Machin J, Whitehouse JM, Horne JE, Fenn K, Ma Y, El Mkami H, Bohringer N, Schaberle TF, Ranson NA, Radford SE, Pliotas C Angew Chem Int Ed Engl. 2023 May 10:e202218783. doi: 10.1002/anie.202218783. PMID:37162386^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.