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bioRxiv · 10.1101/2025.10.16.682720

Structures of folding intermediates on BAM show diverse substrates fold by a uniform mechanism

Thomson, B. D.·Marquez, M. D.·Rawson, S.·dos Santos, T. M. A.·Harrison, S. C.·Kahne, D.
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Abstract

The outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria contain {beta}-barrel membrane proteins that are assembled by conserved multi-subunit machines. In bacteria, the {beta}-barrel assembly machine (BAM) folds over a hundred compositionally different substrates into barrels that vary greatly in size. Some larger barrels require globular proteins to plug the barrel lumen. How a single machine can assemble such different barrels is unknown. Here we report three structures representing progressively folded stages of a 16-stranded barrel engaged with BAM, as well as the structure of a late-stage folding intermediate of a 26-stranded substrate folding around its soluble lipoprotein plug on BAM. We find that BAM catalyzes folding of these substrates by a uniform mechanism in which BAM undergoes major distortions to accommodate the nascent barrel.

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Thomson, B. D., Marquez, M. D., Rawson, S., dos Santos, T. M. A., Harrison, S. C., Kahne, D.. 2025-10-17. Structures of folding intermediates on BAM show diverse substrates fold by a uniform mechanism. https://doi.org/10.1101/2025.10.16.682720

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