Lipoproteins in bacteria: structures and biosynthetic pathways

• Published in: The FEBS journal 2012-12, Vol.279 (23), p.4247-4268
• Main Authors: Nakayama, Hiroshi, Kurokawa, Kenji, Lee, Bok Luel
• Format: Article
• Language: English
• Subjects: Bacteria - genetics; Bacteria - metabolism; Bacterial proteins; Bacteriology; Biochemistry; Biosynthesis; Escherichia coli; Gram-Positive Bacteria - genetics; Gram-Positive Bacteria - metabolism; Gram‐positive bacteria; Lipoproteins; Lipoproteins - genetics; Lipoproteins - metabolism; mass spectrometry; N‐acyltransferase; post‐translational modification; Protein Processing, Post-Translational; Staphylococcus aureus; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; Toll‐like receptor
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.12041

Bacterial lipoproteins are characterized by the presence of a conserved N‐terminal lipid‐modified cysteine residue that allows the hydrophilic protein to anchor onto bacterial cell membranes. These proteins play important roles in a wide variety of bacterial physiological processes, including virulence, and induce innate immune reactions by functioning as ligands of the mammalian Toll‐like receptor 2. We review recent advances in our understanding of bacterial lipoprotein structure, biosynthesis and structure–function relationships between bacterial lipoproteins and Toll‐like receptor 2. Notably, 40 years after the first report of the triacyl structure of Braun's lipoprotein in Escherichia coli, recent intensive MS‐based analyses have led to the discovery of three new lipidated structures of lipoproteins in monoderm bacteria: the lyso, N‐acetyl and peptidyl forms. Moreover, the bacterial lipoprotein structure is considered to be constant in each bacterium; however, lipoprotein structures in Staphylococcus aureus vary between the diacyl and triacyl forms depending on the environmental conditions. Thus, the lipidation state of bacterial lipoproteins, particularly in monoderm bacteria, is more complex than previously assumed. Bacterial lipoproteins have covalently‐linked fatty acids at the N‐terminus, enabling them to anchor on cell membranes and to stimulate host innate immunity. Here, we review recent advances in our understandings of lipoproteins, which include mass spectrometry‐driven determination of novel lipid‐modified structures and environment‐mediated alteration in lipid modifications. These discoveries are now changing the conventional view of bacterial lipoproteins