Decoding of sorting signals by coatomer through a GTPase switch in the COPI coat complex.
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.
Goldberg
J
J
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. jonathan@ximpact4.ski.mskcc.org
D020823:ADP-Ribosylation Factor 1 / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D029681:Arabidopsis Proteins; D001665:Binding Sites / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D016764:Cell Polarity / Q000502:physiology; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D008099:Liver / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D044767:Ubiquitin-Protein Ligases
D029681:Arabidopsis Proteins; D002352:Carrier Proteins; D004151:Dipeptides; D010940:Plant Proteins; D021382:Protein Sorting Signals; C471983:AT2G32950 protein, Arabidopsis; D044767:Ubiquitin-Protein Ligases; D020558:GTP Phosphohydrolases; D020823:ADP-Ribosylation Factor 1; D008239:Lysine