The μ2 Subunit of the Clathrin Adaptor AP‐2 Binds to FDNPVY and YppØ Sorting Signals at Distinct Sites

The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. We have used a combination of surface plasmon resonance and crosslinking with a photoactivated peptide probe to demonstrate the interaction between FDNPVY-containing peptides and the mu2 chain of purified AP-2 clathrin adaptors (the complexes responsible for plasma membrane sorting). We show that recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general YppØ sorting signal, another tyrosine-based sequence also recognized by mu2-adaptin. These results suggest the possibility that low-density lipoprotein receptor uptake may be modulated specifically and independently of other proteins in the clathrin pathway.