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

Cell. 2013 Feb 14;152(4):755-67. doi: 10.1016/j.cell.2012.12.042.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • ADP-Ribosylation Factor 1 / chemistry*
  • ADP-Ribosylation Factor 1 / metabolism
  • Allosteric Regulation
  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Endosomes / metabolism
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Mice
  • Molecular Sequence Data
  • Sequence Alignment
  • Transcription Factor AP-1 / chemistry*
  • Transcription Factor AP-1 / metabolism


  • Liposomes
  • Transcription Factor AP-1
  • ADP-Ribosylation Factor 1

Associated data

  • PDB/4HMY