Chapter 14 Lipoproteins, structure, function, biosynthesis and model for protein export

Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold ‘em, knowing when to fold ‘em

“…Lipid modification is achieved through covalent addition of a diacylglyceride to an indispensable cysteine residue in the lipoprotein signal peptide, as originally described for the prototypical Braun's lipoprotein of Escherichia coli [1]. This provides a common anchoring mechanism for what is now recognized to be an abundant and functionally diverse class of peripheral membrane proteins.…”

“…It had long been assumed, based primarily on studies in E. coli, that all lipoprotein precursors are synthesized with signal peptides that direct them to the Sec pathway for translocation across the cytoplasmic membrane in an unfolded state [1,11]. More recently, it has also become clear that some putative lipoproteins can be translocated utilizing the SecA2-dependent accessory Sec pathway, which is found in some, but not all, Grampositive bacteria [12,13].…”

“…The pathway for bacterial lipoprotein biogenesis was established in E. coli by the pioneering work of Wu and co-workers [1]. After export through Sec (or Tat), a conserved motif (the 'lipobox') in their Type II signal peptides directs these proteins to the lipoprotein biogenesis machinery.…”

“…This lipobox motif is typically L -3 -[A/S/T] -2 -[G/A]--1 -C +1 with the +1 cysteine absolutely conserved in all bacterial lipoproteins ( Figure 1). The thiol chemistry of the cysteine is crucial to this step as the diacylglycerol lipid anchor is added in a thioether linkage [1]. In Gram-negative bacteria, lipoprotein biogenesis is a three step pathway that apparently proceeds in strict order: (i) Prolipoprotein diacylglyceryl transferase (Lgt) uses membrane lipid substrates and catalyses the transfer of a diacylglyceryl moiety onto the conserved lipobox cysteine via a thioether linkage.…”

“…Concluding remarks and future perspectives Our understanding of lipoprotein biogenesis has increased greatly since the pioneering work of Wu and colleagues [1]. Studies with Gram-positive bacteria have revealed that the basic enzymology of Lgt and Lsp are both necessary and sufficient for correct localization of lipoproteins, whereas the extent and significance of N-terminal acylation remains less clear.…”