Outer membrane lipoprotein biogenesis: Lol is not the end

Abstract

Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins are synthesized in precursor form with an N-terminal signal sequence (SS) that targets translocation across the cytoplasmic or inner membrane (IM). Lipid modification and SS processing take place at the periplasmic face of the IM. Outer membrane (OM) lipoproteins take the localization of lipoproteins (Lol) export pathway, which ends with the insertion of the N-terminal lipid moiety into the inner leaflet of the OM. For many lipoproteins, the biogenesis pathway ends here. We provide examples of lipoproteins that adopt complex topologies in the OM that include transmembrane and surface-exposed domains. Biogenesis of such lipoproteins requires additional steps beyond the Lol pathway. In at least one case, lipoprotein sequences reach the cell surface by being threaded through the lumen of a beta-barrel protein in an assembly reaction that requires the heteropentomeric Bam complex. The inability to predict surface exposure reinforces the importance of experimental verification of lipoprotein topology and we will discuss some of the methods used to study OM protein topology.

Comprehensive Spatial Analysis of the Borrelia burgdorferi Lipoproteome Reveals a Compartmentalization Bias toward the Bacterial Surface

“…Whereas the periplasmic OM lipoprotein Lp6.6 is among the most abundant envelope proteins (131), the relative simplicity of the B. burgdorferi lipoproteome in the inner leaflet of the OM is unexpected. In E. coli, an organism with a diderm membrane architecture similar to that of B. burgdorferi, most of the lipoproteins are exported to the OM as well (132), but the majority are not surface exposed (133). A generalization that lipoprotein surface exposure is rare and limited appears to hold for most diderm bacteria, with the emerging exception of the Gram-negative Bacteroidetes, such as Bacteroides fragilis and C. capnocytophaga (43,45).…”

Making a membrane on the other side of the wall

“…The identity of +2 and +3 residues adjacent to the acylated cysteine determine localization [13,14]. Recent reviews have described the current state of knowledge about the Lol pathway and lipoprotein assembly into the OM, including lipoproteins that are surface exposed [15,16]. …”

Outer Membrane Biogenesis

“…Although the Lol pathway, which delivers Lipoproteins to the OM has been well-studied, the final topology of lipoproteins cannot be easily predicted; they can face either the periplasm or the extracellular milieu or they can adopt a transmembrane topology and this final step in lipoprotein biogenesis is the least characterized (53). In contrast, the topology of β-barrels can be easily predicted due to the β-strands with their alternating hydrophobic and polar amino acids (30).…”