Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly.
AP-2 adaptors regulate clathrin-bud formation at the cell surface by recruiting clathrin trimers to the plasma membrane and by selecting certain membrane proteins for inclusion within the developing clathrin-coat structure. These functions are performed by discrete subunits of the adaptor heterotetramer. The carboxyl-terminal appendage of the AP-2 alpha subunit appears to regulate the translocation of several endocytic accessory proteins to the bud site. We have determined the crystal structure of the alpha appendage at 1.4-A resolution by multiwavelength anomalous diffraction phasing. It is composed of two distinct structural modules, a beta-sandwich domain and a mixed alpha-beta platform domain. Structure-based mutagenesis shows that alterations to the molecular surface of a highly conserved region on the platform domain differentially affect associations of the appendage with amphiphysin, eps15, epsin, and AP180, revealing a common protein-binding interface.
Pubmed ID: 10430869 RIS Download
Adaptor Proteins, Vesicular Transport | Amino Acid Sequence | Animals | Clathrin | Crystallography, X-Ray | Humans | Macromolecular Substances | Mice | Models, Molecular | Molecular Sequence Data | Monomeric Clathrin Assembly Proteins | Mutagenesis, Site-Directed | Nerve Tissue Proteins | Phosphoproteins | Protein Structure, Secondary | Recombinant Fusion Proteins