Internalization signals of the Yxx phi type (phi = bulky hydrophobic side chain) interact with the mu 2 chain of AP-2 adaptors. Internalization activity is intolerant of non-conservative substitution of either the tyrosine or the phi side chains, which bind to hydrophobic pockets in mu 2 adaptin in a conformation described as 'a two pinned plug into a socket'. P-selectin, a type I transmembrane protein, contains the Yxx phi-like sequence YGVF in its cytoplasmic domain, but substitution of either the tyrosine or phenylalanine with alanine in the full-length protein causes only small changes in the rate of endocytosis. It is shown here that the sequence YGVF contained within a peptide corresponding to the 17 COOH-terminal amino acids of P-selectin binds to mu 2 adaptin in the same fashion previously seen for other Yxx phi motifs. In addition, the P-selectin peptide binds to a third hydrophobic pocket in mu 2 adaptin through a leucine at position Y-3 in the peptide. This structure suggests that some sequences can function as a 'three pinned plug', in which internalization activity is not critically dependent on any one of the three interacting side chains.

• PMID: 11247301
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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, Non-P.H.S. | Research Support, U.S. Gov't, P.H.S.

Authors

Owen DJ, Setiadi H, Evans PR, McEver RP, Green SA

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