Dileucine

Dileucine can refer to two related concepts in biochemistry and cell biology. In peptide chemistry, it denotes the dipeptide composed of two leucine residues (Leu-Leu). In cell biology, it denotes a class of sorting signals found in the cytoplasmic tails of some transmembrane proteins, which influence intracellular trafficking, including endocytosis and sorting between the trans-Golgi network and endosomes.

Sorting motif details: The canonical dileucine motif is a short sequence typically described as [DE]XXXL[LI] or D/E XXX LL, in which an acidic residue (aspartate or glutamate) precedes three any residues and a pair of leucines (LL) or a leucine-isoleucine pair at the end. The motif is usually positioned in the cytoplasmic side of the membrane, close to the transmembrane domain, and is accessible to cytosolic adaptor proteins.

Mechanism and function: Dileucine signals are recognized by clathrin adaptor protein complexes AP-1, AP-2, and AP-3, which recruit clathrin and drive vesicle formation for endocytosis or sorting from the Golgi to endosomes. Spacing and surrounding residues influence recognition, and variants exist with one leucine replaced by isoleucine or with different spacer lengths. These motifs can operate together with other sorting signals, such as tyrosine-based motifs, to determine the precise itinerary of cargo proteins.

Examples and prevalence: Dileucine motifs are common in a range of cargo proteins, including transporters and receptors, where proper trafficking is essential for cellular function. The motif’s use highlights the role of short linear motifs in regulating membrane trafficking.

As a dipeptide, dileucine (Leu-Leu) occurs naturally as part of protein sequences and, like other dipeptides, contributes to hydrophobic interactions in proteins or can be studied in synthetic peptides.