bamD

BamD is a periplasmic lipoprotein that is a core component of the beta-barrel assembly machinery (BAM) in Gram-negative bacteria. It participates in the folding and insertion of outer membrane beta-barrel proteins (OMPs) into the outer membrane. BamD is encoded by the bamD gene and is widely conserved among proteobacteria and other Gram-negative lineages.

Like other BAM components, BamD is exported via the Sec pathway, modified by lipoprotein signal peptidase II, and anchored to the periplasmic face of the outer membrane by an N-terminal lipid moiety. It contains multiple tetratricopeptide repeat (TPR) motifs that form a curved, horseshoe-shaped domain, enabling extensive protein–protein interactions within the BAM complex.

BamD interacts with BamA and other BAM subunits and is thought to play a key role in recognizing substrates and coordinating their delivery to BamA for folding and insertion. It helps determine the efficiency and fidelity of OMP assembly for a broad set of outer membrane proteins, including beta-barrel porins.

Genetic studies in Escherichia coli have shown that BamD is essential for proper outer membrane biogenesis and viability in many strains; depletion or defects in BamD lead to accumulation of misfolded OMPs, increased membrane permeability, and growth defects. The essentiality can vary among species and genetic backgrounds.

Because the BAM pathway is critical for outer membrane integrity, BamD and the BAM complex are considered attractive targets for developing antibiotics aimed at compromising the barrier function of Gram-negative bacteria.