Structure and function of the beta‐barrel assembly machine and its chaperones (224.2)

Abstract

Transmembrane proteins in the bacterial outer membrane display a characteristic beta‐barrel architecture. Folding and insertion of these Outer Membrane Proteins (OMPs) is essential for Gram‐Negative bacteria and requires the action of both periplasmic chaperones and the outer membrane complex known as beta‐Barrel Assembly Machine (BAM). The BAM complex is composed of BamA, a bετα‐barrel OMP itself; and four associated lipoproteins: BamB, C, D and E. BamA and BamD are essential for viability and appear to be present in all bacteria with an outer membrane. Whereas the phylogenetic distribution of BamB, C and E is not well defined, these lipoproteins are also important for OMP biogenesis and their deletion in E. coli results in outer membrane permeability defects. I present the crystal and NMR structures of BAM subunits as well as a complex between BamB and a periplasmic fragment of BamA, which begin to illuminate the architecture of this essential molecular machine. We show that chaperones prevent nascent OMP aggregation in the periplasm and maintain them in an unfolded state. The central BAM component, BamA, undergoes conformational transitions that are essential for its role in OMP folding and insertion, whereas BamB is proposed to modulate these conformational changes.