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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 ?1 subunit of one AP-1 complex, while the back side of Arf1 binds to the central part of the ? subunit trunk of a second AP-1 complex. A third Arf1 interaction site near the N terminus of the ? subunit is important for recruitment, but not activation. These observations lead to a model for the recruitment and activation of AP-1 by Arf1.

SUBMITTER: Ren X

PROVIDER: S-EPMC3913725 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Structural basis for recruitment and activation of the AP-1 clathrin adaptor complex by Arf1.

Ren Xuefeng X Farías Ginny G GG Canagarajah Bertram J BJ Bonifacino Juan S JS Hurley James H JH

Cell 20130201 4

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 ter ...[more]

PMID: 23415225

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