A Structural Explanation for the Binding of Multiple Ligands by the α-Adaptin Appendage Domain
The α 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 Å resolution crystal structure of this domain reveals a single binding site for its ligands, which include amphiphysin, Eps15, and epsi...
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| Veröffentlicht in: | Cell 1999-06, Vol.97 (6), p.805-815 |
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| container_title | Cell |
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| creator | Owen, David J. Vallis, Yvonne Noble, Martin E.M. Hunter, Jack B. Dafforn, Tim R. Evans, Philip R. McMahon, Harvey T. |
| description | The α 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 Å 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. |
| doi_str_mv | 10.1016/S0092-8674(00)80791-6 |
| format | Article |
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| fulltext | fulltext |
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| ispartof | Cell, 1999-06, Vol.97 (6), p.805-815 |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adaptor Protein Complex 2 Adaptor Protein Complex alpha Subunits Adaptor Proteins, Vesicular Transport Amino Acid Sequence Animals Binding Sites COS Cells Crystallography, X-Ray Endocytosis Ligands Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Molecular Sequence Data Protein Conformation |
| title | A Structural Explanation for the Binding of Multiple Ligands by the α-Adaptin Appendage Domain |
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