Outer Membrane Biogenesis

Abstract

The hallmark of Gram-negative bacteria and organelles such as mitochondria and chloroplasts is the presence of an outer membrane (OM). In bacteria such as Escherichia coli, the OM is a unique asymmetric lipid bilayer with lipopolysaccharide (LPS) in the outer leaflet. Integral, transmembrane proteins assume a β-barrel structure (OMPs) and their assembly is catalyzed by the heteropentomeric Bam complex containing the OMP BamA and four lipoproteins, BamB-E. How the Bam complex assembles a great diversity of OMPs into a membrane without an obvious energy source is a particularly challenging problem because folding intermediates are predicted to be unstable in either an aqueous or a hydrophobic environment. Two models have been put forward, the budding model based largely on structural data, and the BamA-assisted model based on genetic and biochemical studies. Here we offer a critical discussion of the pros and cons of each.

Two pKM101‐encoded proteins, the pilus‐tip protein TraC and Pep, assemble on the Escherichia coli cell surface as adhesins required for efficient conjugative DNA transfer

“…The BAM complex and its role in insertion of β-barrel proteins into the OM has been defined in considerable structural and mechanistic detail (Konovalova et al, 2017;Noinaj et al, 2017). There is also increasing appreciation that the BAM complex plays a broader role in crafting the protein landscape at the cell surface (Pavlova et al, 2013;Konovalova et al, 2014;Bernstein, 2015).…”

Constructing and deconstructing the bacterial cell wall

“…Intimate structural synergy is now recognized between the peptidoglycan and the teichoic acids of the Gram‐positive bacteria, and between the peptidoglycan and the outer membrane of the Gram‐negative bacteria . Indeed, new opportunities for antibiotic discovery have been identified that interfere with teichoic acid integration into the cell wall of Gram‐positive bacteria and with respect to lipopolysaccharide transport in Gram‐negative bacteria . Within this universe of opportunity, we exemplify our own efforts toward the mechanistic and structural understanding of key enzymes of the bacteria with roles in cell envelope biosynthesis and antibiotic resistance.…”

“…77,78 Indeed, new opportunities for antibiotic discovery have been identified that interfere with teichoic acid integration into the cell wall of Gram-positive bacteria 69,[79][80][81][82][83][84] and with respect to lipopolysaccharide transport in Gram-negative bacteria. [85][86][87][88][89][90] Within this universe of opportunity, we exemplify our own efforts toward the mechanistic and structural understanding of key enzymes of the bacteria with roles in cell envelope biosynthesis and antibiotic resistance.…”

A simple protocol to characterize bacterial cell‐envelope lipoproteins in a native‐like environment

“…These membranes have diverse lipid compositions and are active participants in essential biological processes . The outer membrane of Gram‐negative bacteria is the first of the three layers that surround the bacterial cytoplasm . This bilayer is highly asymmetric: the inner leaflet is mainly built by various species of phospholipids, while the outer leaflet is largely composed of lipopolysaccharides (LPS) .…”

“…Biological processes taking place in the bacterial cell envelope are mainly related to the communication of the cell with the external medium, which includes sensing and providing feedback to external conditions . Proteins located within the bacterial cell envelope, including integral membrane proteins, lipidated proteins, peripheral membrane proteins, and soluble proteins, play key roles in these communication events . Lipidated proteins are anchored to biological membranes through a lipid moiety covalently bound to their N‐termini and represent 2–8% of the total predicted proteome in bacteria …”