title: A structural explanation for the binding of multiple ligands by the alpha-adaptin appendage domain.
abstract: The alpha subunit of the endocytotic AP2 adaptor complex contains a 30 kDa "appendage" domain, which is joined to the rest of the protein via a flexible linker. The 1.9 A resolution crystal structure of this domain reveals a single binding site for its ligands, which include amphiphysin, Eps15, and epsin. This domain when overexpressed in COS7 fibroblasts is shown to inhibit transferrin uptake, whereas mutants in which interactions with its binding partners are abolished do not. DPF/W motifs present in appendage domain-binding partners are shown to play a crucial role in their interactions with the domain. A single site for binding multiple ligands would allow for temporal and spatial regulation in the recruitment of components of the endocytic machinery.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: D J
authors.initials: DJ
authors.lastname: Owen
authors.forename: Y
authors.initials: Y
authors.lastname: Vallis
authors.forename: M E
authors.initials: ME
authors.lastname: Noble
authors.forename: J B
authors.initials: JB
authors.lastname: Hunter
authors.forename: T R
authors.initials: TR
authors.lastname: Dafforn
authors.forename: P R
authors.initials: PR
authors.lastname: Evans
authors.forename: H T
authors.initials: HT
authors.lastname: McMahon
mesh_terms: D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D018360:Crystallography, X-Ray; D004705:Endocytosis; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D008024:Ligands; D008565:Membrane Proteins