Sequence requirements for the recognition of tyrosine-based endocytic signals by clathrin AP-2 complexes Academic Article uri icon


MeSH Major

  • Clathrin
  • DNA-Binding Proteins
  • Endocytosis
  • Protein Sorting Signals
  • Transcription Factors


  • We recently determined that fusion proteins containing tyrosine-based endocytic signals bind to the mu 2 subunit of AP-2, the complex that drives clathrin coat formation and mediates endocytosis from the plasma membrane. Here we analyze the selectivity of peptide recognition by mu 2 and by AP-2 using combinatorial selection methods and surface plasmon resonance. Both mu 2 and AP-2 are shown to interact with various sequences of the form tyrosine-polar-polar-hydrophobic (Yppø) found on receptors that follow the clathrin pathway. The optimal sequence for interaction with mu 2 and with AP-2 has tyrosine as an anchor and prefers arginine at position Y + 2 and leucine at position Y + 3. In contrast, no preferred sequence is detected surrounding the Yppø signal, indicating that recognition of the Yppø endocytic signal does not require a prefolded structure. We conclude that sorting into the endocytic pathway is governed by a surprisingly simple interaction between the mu 2 chain and a tyrosine-containing tetrapeptide sequence.

publication date

  • November 1996



  • Academic Article



  • eng

PubMed Central ID

  • PMC452326

PubMed ID

  • 8918456

Additional Document Info

start page

  • 5789

end page

  • 95


  • 15


  • 21