lipoboxmotif

The lipobox motif, or lipobox, is a conserved short sequence found at the end of signal peptides in many bacterial lipoproteins. This motif marks the site where the signal peptide is processed and where lipid modification occurs, enabling the mature protein to anchor to the membrane.

The most commonly cited lipobox consensus is L-[VI]-[ASTVI]-C, with a cysteine serving as the lipidated residue after processing. However, there is variability among species, and different lipobox sequences can appear in nature. The key functional feature is the cysteine residue that becomes lipidated, rather than an exact sequence in all cases.

Processing of lipoproteins involves a series of enzymes. The diacylglycerol transferase Lgt first attaches a diacylglycerol group to the thiol of the lipobox cysteine. Signal peptidase II, LspA, cleaves the signal peptide immediately downstream of the lipobox, exposing the lipidated cysteine. In many Gram-negative bacteria, the enzyme Lnt then adds an acyl group to the amino terminus of the lipidated cysteine, producing a triacylated lipoprotein. In Gram-positive bacteria, lipid modification pathways can differ and some lipoproteins may remain diacylated.

Functionally, lipobox-containing lipoproteins are typically anchored to the inner membrane and participate in diverse processes, including nutrient transport, cell wall remodeling, signaling, and interactions with the environment. They can be essential for virulence in certain pathogens and are common targets for comparative genomics and structural studies.

In research, the lipobox motif is used to predict lipoproteins from genomic data. While useful, predictions can be complicated by sequence variability and atypical motifs, requiring experimental validation for confirmation.