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Chapter 6 : Lipoproteins and Their Trafficking to the Outer Membrane

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Abstract:

Lipoproteins are a family of secreted proteins that are acylated after their translocation across the plasma membrane ( ). Acylation spatially confines lipoproteins by anchoring them into membranes. Lipoproteins are bioinformatically identifiable by the highly conserved lipobox motif in their short signal peptides ( ). Within the lipobox is a cleavage site for signal peptidase II (SPII; Lsp). Immediately adjacent is an invariant Cys residue which is the target of acylation reactions. Most lipoproteins are secreted from the cytosol via the SecYEG translocon ( ), though secretion via the twin-arginine transport (Tat) system has also been identified ( ). Following translocation, the inner membrane (IM) enzyme Lgt attaches a diacyl moiety to the lipobox Cys of prolipoproteins via a thioester linkage ( Fig. 1 ) ( ). The diacylated product is a substrate for Lsp, which releases the apolipoprotein from its signal peptide ( Fig. 1 ) ( ). The diacylated Cys residue then becomes the first amino acid of the lipoprotein (Cys). In Gram-negative bacteria, a third acyl group is attached by the enzyme Lnt to the Cys amino group (which was made available following Lsp cleavage) ( Fig. 1 ) ( ). The acyl chain donors in Lgt and Lnt reactions are plasma membrane phospholipids ( Fig. 1 ). Gram-negative bacteria produce triacylated lipoproteins; , , and are therefore conserved and essential in the majority of these organisms. Low-GC Gram-positive bacteria lack homologs and generate considerable diversity in lipoprotein acylation; in addition to the triacyl form, these bacteria can variously generate diacyl, lyso, peptidyl, and -acetyl lipoprotein forms ( ) ( Fig. 1 ). How such diversity is generated largely awaits discovery, although recent progress has identified the enzyme, Lit, that is responsible for producing lyso-form lipoproteins in and ( ).

Citation: Grabowicz M. 2019. Lipoproteins and Their Trafficking to the Outer Membrane, p 67-76. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0038-2018
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Figure 1

Secreted lipoproteins are first diacylated at an invariant Cys residue by Lgt using resident phospholipids as acyl donors. The signal sequence is then cleaved by the peptidase Lsp to yield diacyl-form lipoproteins. In almost all Gram-negative bacteria, Lnt attaches another acyl chain to the amino group of Cys to yield triacyl-form lipoproteins. Low-GC Gram-negative bacteria can also produce peptidyl forms (likely due to an Lsp-type enzyme that yields Cys), as well as -acetyl and lyso forms that are derived from diacyl lipoproteins. Triacyl- and lyso-lipoproteins can efficiently interact with LolCDE for trafficking to the OM in Gram-negative organisms. Diacyl-form lipoproteins can be trafficked to the OM via LolDF.

Citation: Grabowicz M. 2019. Lipoproteins and Their Trafficking to the Outer Membrane, p 67-76. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0038-2018
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Image of Figure 2
Figure 2

The OM lipoprotein trafficking routes of are shown. Once mature, OM-targeted lipoproteins engage with the LolCDE transporter in the IM. LolE interacts with lipoproteins and LolC recruits the periplasmic chaperone protein LolA. At the expense of ATP hydrolysis by LolD, the LolCDE complex extracts lipoproteins from the IM bilayer and transfers them to LolA. Lipoproteins are shuttled through the periplasm in a LolA-bound complex. At the OM, the lipoprotein LolB receives LolA-bound client lipoproteins and anchors them into the OM bilayer. Since Δ mutants are viable, an alternate trafficking route must exist that can traffic essential OM lipoproteins to support cell viability. LolCDE remains essential in such Δ mutants, suggesting that lipoproteins originate from this complex and are then trafficked to the OM via an unknown mechanism.

Citation: Grabowicz M. 2019. Lipoproteins and Their Trafficking to the Outer Membrane, p 67-76. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0038-2018
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