title: Structural basis for recruitment and activation of the AP-1 clathrin adaptor complex by Arf1.
abstract: AP-1 is a clathrin adaptor complex that sorts cargo between the trans-Golgi network and endosomes. AP-1 recruitment to these compartments requires Arf1-GTP. The crystal structure of the tetrameric core of AP-1 in complex with Arf1-GTP, together with biochemical analyses, shows that Arf1 activates cargo binding by unlocking AP-1. Unlocking is driven by two molecules of Arf1 that bridge two copies of AP-1 at two interaction sites. The GTP-dependent switch I and II regions of Arf1 bind to the N terminus of the β1 subunit of one AP-1 complex, while the back side of Arf1 binds to the central part of the γ subunit trunk of a second AP-1 complex. A third Arf1 interaction site near the N terminus of the γ subunit is important for recruitment, but not activation. These observations lead to a model for the recruitment and activation of AP-1 by Arf1.
authors: Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Xuefeng
authors: X
authors: Ren
authors: Ginny G
authors: GG
authors: Farías
authors: Bertram J
authors: BJ
authors: Canagarajah
authors: Juan S
authors: JS
authors: Bonifacino
authors: James H
authors: JH
authors: Hurley
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000737:chemistry* / Q000378:metabolism; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D018808:Transcription Factor AP-1 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008081:Liposomes; D018808:Transcription Factor AP-1; D020823:ADP-Ribosylation Factor 1