Definition of the Consensus Motif Recognized by - Adaptin Ear Domains

The heterotetrameric adaptor complex 1 (AP-1) and the monomeric Golgi-localized, ear-containing, Arfbinding (GGA) proteins are components of clathrin coats associated with the trans-Golgi network and endosomes. The carboxyl-terminal ear domains (or -adaptin ear (GAE) domains) of two -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 G(P/D/E)( /L/M) (where 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.