Cell
Volume 152, Issue 4, 14 February 2013, Pages 755-767
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Article
Structural Basis for Recruitment and Activation of the AP-1 Clathrin Adaptor Complex by Arf1

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Summary

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.

Highlights

► Crystal structure of the AP-1 clathrin adaptor complex bound to Arf1 ► Arf1 promotes the open conformation and cargo binding by AP-1 ► AP-1 is recruited via canonical Arf1 contacts with β and γ subunits ► AP-1 is activated by dimerizing via the back side of Arf1

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