title: Recognition of accessory protein motifs by the gamma-adaptin ear domain of GGA3.
abstract: Adaptor proteins load transmembrane protein cargo into transport vesicles and serve as nexuses for the formation of large multiprotein complexes on the nascent vesicles. The gamma-adaptin ear (GAE) domains of the AP-1 adaptor protein complex and the GGA adaptor proteins recruit accessory proteins to these multiprotein complexes by binding to a hydrophobic motif. We determined the structure of the GAE domain of human GGA3 in complex with a peptide based on the DFGPLV sequence of the accessory protein Rabaptin-5 and refined it at a resolution of 2.2 A. The leucine and valine residues of the peptide are partly buried in two contiguous shallow, hydrophobic depressions. The anchoring phenylalanine is buried in a deep pocket formed by the aliphatic portions of two conserved arginine residues, along with an alanine and a proline, illustrating the unusual function of a cluster of basic residues in binding a hydrophobic motif.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Miller
authors.forename: Rafael
authors.initials: R
authors.lastname: Mattera
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
authors.forename: James H
authors.initials: JH
authors.lastname: Hurley
mesh_terms: D020727:ADP-Ribosylation Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D033961:Adaptor Protein Complex 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D033982:Adaptor Protein Complex gamma Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D033961:Adaptor Protein Complex 1; D033982:Adaptor Protein Complex gamma Subunits; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C407306:GGA adaptor proteins; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D020727:ADP-Ribosylation Factors