Identification and characterization of lipid-modified proteins in bacteria

Abstract

Abstract Covalent modification of membrane proteins with lipids is ubiquitous in all living cells. Research on the biosynthesis of lipoproteins has been focused mainly on the major outer membrane (Braun’s) lipoprotein of Escherichia coli as a prototype of all other bacterial lipoproteins (lipid-modified proteins) (for a recent review of bacterial lipoproteins, see ref. 1). Braun’s lipoprotein is first synthesized as a precursor protein-the unmodified prolipoprotein that contains a signal sequence with a cleavage site of Leu-Ala-Gly-Cys. More generally, the sequence of Leu-(Ala, Ser)-(Gly, Ala)-Cys is found at the -3 to +1 positions of the prolipoprotein modification/processing site in about three-fourths of all lipoprotein signal sequences in bacteria, as indicated by an analysis of the signal sequences of twenty-six distinct bacterial lipoprotein precursors (1). The unmodified prolipoprotein with this consensus sequence undergoes sequential modifications and processing catalysed by glyceryl transferase, 0-acyl transferase(s), prolipoprotein signal peptidase (signal peptidase II), and N-acyl transferase, in that order, to form the mature lipoprotein containing N-acyl diglyceride-cysteine at its amino-terminus (2).