RESUMO
Gram-negative bacteria express structurally diverse lipoproteins in their cell envelope. Here, we find that approximately half of lipoproteins destined to the Escherichia coli outer membrane display an intrinsically disordered linker at their N terminus. Intrinsically disordered regions are common in proteins, but establishing their importance in vivo has remained challenging. As we sought to unravel how lipoproteins mature, we discovered that unstructured linkers are required for optimal trafficking by the Lol lipoprotein sorting system, whereby linker deletion re-routes three unrelated lipoproteins to the inner membrane. Focusing on the stress sensor RcsF, we found that replacing the linker with an artificial peptide restored normal outer-membrane targeting only when the peptide was of similar length and disordered. Overall, this study reveals the role played by intrinsic disorder in lipoprotein sorting, providing mechanistic insight into the biogenesis of these proteins and suggesting that evolution can select for intrinsic disorder that supports protein function.
Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Proteínas Intrinsicamente Desordenadas/metabolismo , Lipoproteínas/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/fisiologia , Proteínas Intrinsicamente Desordenadas/química , Lipoproteínas/genética , Modelos Moleculares , Conformação Proteica , Transporte ProteicoRESUMO
Bacterial lipoproteins are globular proteins anchored to a membrane by a lipid moiety. By discovering new functions carried out by lipoproteins, recent research has highlighted the crucial roles played by these proteins in the cell envelope of Gram-negative bacteria. Here, after discussing the wide range of activities carried out by lipoproteins in the model bacterium Escherichia coli, we review new insights into the essential mechanisms involved in lipoprotein maturation, sorting and targeting to their final destination. A special attention will also be given to the recent identification of lipoproteins on the surface of E. coli and of other bacteria. The renewed interest in lipoproteins is driven by the need to identify novel targets for antibiotic development.
