The structure of an endocytosis signal.

The efficient endocytosis of transmembrane receptor proteins requires a signal sequence in the cytoplasmic domain of the protein to promote clustering into coated pits. Analysis of the clustering of receptors with natural or engineered mutations in their cytoplasmic domains implicates an aromatic residue in a particular context as the necessary clustering signal. Recent detailed studies of mutants have led to computer predictions of a plausible structural motif. These predictions have now been elegantly supported by using NMR to determine the structure of synthetic peptides. New evidence that this sorting signal performs multiple functions suggests that this may not be the whole story.