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Sequence requirements for the recognition of tyrosine‐based endocytic signals by clathrin AP‐2 complexes.
Author(s) -
Boll W.,
Ohno H.,
Songyang Z.,
Rapoport I.,
Cantley L. C.,
Bonifacino J. S.,
Kirchhausen T.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00965.x
Subject(s) - endocytic cycle , biology , tyrosine , clathrin , clathrin adaptor proteins , endocytosis , tetrapeptide , protein sorting signals , microbiology and biotechnology , biochemistry , peptide sequence , signal peptide , peptide , receptor , gene
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.