Lipid-regulated assembly mechanisms and functional energetics of the essential bacterial chaperone BamA.

ABSTRACT: BamA is a highly conserved essential outer membrane chaperone of all Gram-negative bacteria. Our understanding of the BamA machinery remains incomplete, delaying knowledge-based antibacterial design. Here, we report the first detailed identification of molecular elements indispensable for BamA folding, stability, and function. BamA displays two unique transition state structures and folding pathways in phosphatidylethanolamine (PE)- and phosphatidylglycerol (PG)-containing membranes. PE retards BamA folding; once folded, PE lowers stability of the N-terminal β-strands. In interesting contrast, PG promotes directional folding of BamA, and rigidifies the protein structure by lowering its conformational sampling space. We demonstrate that BamA β5-L4-β8 is an obligatory late-assembly zone in b

SUBMITTER: George A 

PROVIDER: S-EPMC12712708 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature