Decoding of sorting signals by coatomer through a GTPase switch in the COPI coat complex

Cell. 2000 Mar 17;100(6):671-9. doi: 10.1016/s0092-8674(00)80703-5.


Sorting signals on cargo proteins are recognized by coatomer for selective uptake into COPI (coatomer)-coated vesicles. This study shows that coatomer couples sorting signal recognition to the GTP hydrolysis reaction on ARF1. Coatomer responds differently to different signals. The cytoplasmic signal sequence of hp24a inhibits coatomer-dependent GTP hydrolysis. By contrast, the dilysine retrieval signal, which competes for the same binding site on coatomer, has no effect on GTPase activity. It is inferred that, in vivo, sorting signal selection is under kinetic control, with coatomer governing a GTPase discard pathway that excludes dilysine-tagged proteins from one class of COPI-coated vesicles. The concept of competing sets of sorting signals that act positively and negatively during vesicle budding through a GTPase switch in the COPI coat complex suggests mechanisms for cargo segregation in which specificity is conferred by GTP hydrolysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-Ribosylation Factor 1 / chemistry
  • ADP-Ribosylation Factor 1 / metabolism*
  • Amino Acid Sequence
  • Animals
  • Arabidopsis Proteins*
  • Binding Sites / physiology
  • Biological Transport / physiology
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cattle
  • Cell Polarity / physiology
  • Cytoplasmic Granules / chemistry
  • Cytoplasmic Granules / metabolism
  • Dipeptides / metabolism
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / metabolism*
  • Hydrolysis
  • Liver / chemistry
  • Liver / cytology*
  • Liver / enzymology
  • Lysine / metabolism
  • Molecular Sequence Data
  • Plant Proteins / chemistry
  • Plant Proteins / metabolism*
  • Protein Sorting Signals / chemistry
  • Protein Sorting Signals / metabolism*
  • Protein Structure, Tertiary
  • Ubiquitin-Protein Ligases*


  • Arabidopsis Proteins
  • Carrier Proteins
  • Dipeptides
  • Plant Proteins
  • Protein Sorting Signals
  • AT2G32950 protein, Arabidopsis
  • Ubiquitin-Protein Ligases
  • GTP Phosphohydrolases
  • ADP-Ribosylation Factor 1
  • Lysine