Work

Conformational Plasticity of LptC Regulates Lipopolysaccharide Transport by the LptB 2 FGC Complex

Year: 2025

Type: article

Abstract: The outer membrane of Gram-negative bacteria is coated with lipopolysaccharide (LPS). The Lpt system maintains membrane asymmetry by transporting LPS from the inner to the outer membrane. Transport begins with the LptB₂FGC complex, where the ABC transporter LptB₂FG associates with LptC to extract LPS. LPS is then passed via LptA to the LptDE translocon. While LptB₂FGC structures suggest an extrusion mechanism, the role of LptC remains unclear. Here, we reconstituted the complex in vitro from purified LptB₂FG and LptC, and demonstrate that LptC stabilizes the complex and modulates ATPase activity. Using differential isotope labeling and solid-state NMR including dynamic nuclear polarization, we observed that the LptC transmembrane helix LptC TMH is tightly associated with the transporter in the apo state. Upon LPS or ATP binding, LptC TMH becomes dynamic, favoring cavity collapse and substrate-coupled ATPase activity. Our data support a model in which LptC acts as a mechanical transducer linking transport and energy consumption.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5c11923