Disulfide Rearrangement Triggered by Translocon Assembly Controls Lipopolysaccharide Export

Abstract

Get Ready, Assemble, Fold The outer membrane protein complex LptD/E is responsible for lipopolysaccharide export to the cell surface of Escherichia coli. LptD is an essential β-barrel protein that contains two disulfide bonds between nonconsecutive cysteines. Chng et al. (p. 1665 , published online 30 August) describe the characterization of the oxidative folding and assembly pathway of LptD/E in living cells. A combination of steady-state and pulse-chase measurements was used to identify seven intermediates with different disulfide-bonded states, along the oxidative folding pathway. During folding and assembly, a non-native disulfide-bonded LptD intermediate accumulated and, triggered by β-barrel assembly and association with the lipoprotein LptE, rearranged to the native disulfide-bonded state required for lipopolysaccharide export. Thus, disulfide bond–dependent protein folding can involve the proper assembly of a two-protein complex in order to promote disulfide bond rearrangement.