Outer membrane protein biogenesis in Gram-negative bacteria

Abstract

Gram-negative bacteria contain a double membrane which serves for both protection and for providing nutrients for viability. The outermost of these membranes is called the outer membrane (OM), and it contains a host of fully integrated membrane proteins which serve essential functions for the cell, including nutrient uptake, cell adhesion, cell signalling and waste export. For pathogenic strains, many of these outer membrane proteins (OMPs) also serve as virulence factors for nutrient scavenging and evasion of host defence mechanisms. OMPs are unique membrane proteins in that they have a β-barrel fold and can range in size from 8 to 26 strands, yet can still serve many different functions for the cell. Despite their essential roles in cell survival and virulence, the exact mechanism for the biogenesis of these OMPs into the OM has remained largely unknown. However, the past decade has witnessed significant progress towards unravelling the pathways and mechanisms necessary for moulding a nascent polypeptide into a functional OMP within the OM. Here, we will review some of these recent discoveries that have advanced our understanding of the biogenesis of OMPs in Gram-negative bacteria, starting with synthesis in the cytoplasm to folding and insertion into the OM.

The POTRA domains of Toc75 exhibit chaperone-like function to facilitate import into chloroplasts

“…Given the conservation of key features, these structures serve as models for Toc75, albeit with low sequence identity (7%, 7%, and 8%, respectively). Whereas TamA and BamA have roles in the biogenesis of β-barrel outer membrane proteins in Gram-negative bacteria (23,(52)(53)(54)(55), FhaC has a role in the secretion of filamentous hemagglutinin (FHA) out of Bordetella pertussis (56). Here FhaC serves as the translocon within the outer membrane, first interacting with FHA via its TPS domain and then translocating FHA through its barrel domain, across the outer membrane, and into the extracellular milieu.…”

Syphilis

“…The opening of the channel is covered by a ‘dome’ comprising three extracellular loops, one of which contains an opsonic target that is sequence variable among T. pallidum strains 85 . BamA is the essential central component of the molecular machine that catalyses insertion of newly exported outer membrane proteins to the outer membrane 86 .…”

From Chaperones to the Membrane with a BAM!

“…Interestingly, the potential similarities for insertion of LPS and OMPs by lateral opening of LptD and BamA, respectively, suggests the two major components of the OM may be assembled by similar mechanisms. The observation that BamA laterally opens has prompted the suggestion that BamA provides a template to assist uOMPs in folding [53,57], however no experimental evidence has been published to date that supports this mechanistic interpretation. Additionally, BamA is unlikely to provide conformational instructions for uOMP folding, as uOMPs can attain their native folded states in the absence of BamA in vitro .…”