ArfGAP1 interacts with coat proteins through tryptophan-based motifs

Biochem Biophys Res Commun. 2010 Apr 9;394(3):553-7. doi: 10.1016/j.bbrc.2010.03.017. Epub 2010 Mar 6.


The Arf1 GTPase-activating protein ArfGAP1 regulates vesicular traffic through the COPI system. This protein consists of N-terminal catalytic domain, lipid packing sensors (the ALPS motifs) in the central region, and a carboxy part of unknown function. The carboxy part contains several diaromatic sequences that are reminiscent of motifs known to interact with clathrin adaptors. In pull-down experiments using GST-fused peptides from rat ArfGAP1, a peptide containing a (329)WETF sequence interacted strongly with clathrin adaptors AP1 and AP2, whereas a major coatomer-binding determinant was identified within the extreme carboxy terminal peptide ((405)AADEGWDNQNW). Mutagenesis and peptide competition experiments revealed that this determinant is required for coatomer binding to full-length ArfGAP1, and that interaction is mediated through the delta-subunit of the coatomer adaptor-like subcomplex. Evidence for a role of the carboxy motif in ArfGAP1-coatomer interaction in vivo is provided by means of a reporter fusion assay. Our findings point to mechanistic differences between ArfGAP1 and the other ArfGAPs known to function in the COPI system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 1 / metabolism
  • Adaptor Protein Complex 2 / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Coat Protein Complex I / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Rats
  • Tryptophan / genetics
  • Tryptophan / metabolism


  • Adaptor Protein Complex 1
  • Adaptor Protein Complex 2
  • Arfgap1 protein, rat
  • Coat Protein Complex I
  • GTPase-Activating Proteins
  • Tryptophan