Definition of the Consensus Motif Recognized by γ-Adaptin Ear Domains

• Published in: The Journal of biological chemistry 2004-02, Vol.279 (9), p.8018-8028
• Main Authors: Mattera, Rafael, Ritter, Brigitte, Sidhu, Sachdev S., McPherson, Peter S., Bonifacino, Juan S.
• Format: Article
• Language: English
• Subjects: Adaptor Protein Complex 1; Adaptor Protein Complex gamma Subunits - chemistry; Adaptor Protein Complex gamma Subunits - metabolism; Adaptor Proteins, Vesicular Transport; Amino Acid Sequence; Animals; Binding Sites; Biotinylation; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Clathrin - metabolism; Consensus Sequence; Glutathione Transferase - genetics; Green Fluorescent Proteins; Humans; Luminescent Proteins - genetics; Mice; Microscopy, Fluorescence; Molecular Sequence Data; Mutagenesis; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Library; Recombinant Fusion Proteins; Saccharomyces cerevisiae; Structure-Activity Relationship; Two-Hybrid System Techniques
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M311873200

The heterotetrameric adaptor complex 1 (AP-1) and the monomeric Golgi-localized, γ ear-containing, Arf-binding (GGA) proteins are components of clathrin coats associated with the trans-Golgi network and endosomes. The carboxyl-terminal ear domains (or γ-adaptin ear (GAE) domains) of two γ-adaptin subunit isoforms of AP-1 and of the GGAs are structurally similar and bind to a common set of accessory proteins. In this study, we have systematically defined a core tetrapeptide motif ΨG(P/D/E)(Ψ/L/M) (where Ψ is an aromatic residue), which is responsible for the interactions of accessory proteins with GAE domains. The definition of this motif has allowed us to identify novel GAE-binding partners named NECAP and aftiphilin, which also contain clathrin-binding motifs. These findings shed light on the mechanism of accessory protein recruitment to trans-Golgi network and endosomal clathrin coats.