GGA1 interacts with the adaptor protein AP-1 through a WNSF sequence in its hinge region.
The Golgi-associated gamma-adaptin-related ADP-ribosylation factor-binding proteins (GGAs) are critical components of the transport machinery that mediates the trafficking of the mannose 6-phosphate receptors and associated cargo from the trans-Golgi network to the endosomes. The GGAs colocalize in vivo with the clathrin adaptor protein AP-1 and bind to AP-1 in vitro, ... suggesting that the two proteins may cooperate in packaging the mannose 6-phosphate receptors into clathrin-coated vesicles at the trans-Golgi network. Here, we demonstrate that the sequence, (382)WNSF(385), in the hinge region of GGA1 mediates its interaction with the AP-1 gamma-ear. The Trp and Phe constitute critical amino acids in this interaction. The binding of Rabaptin5 to the AP-1 gamma-ear, which occurs through a FXXPhi motif, is inhibited by a peptide encoding the GGA1 (382)WNSF(385) sequence. Moreover, mutations in the AP-1 gamma-ear that abolish its interaction with Rabaptin5 also preclude its association with GGA1. These results suggest that the GGA1 WXXF-type and Rabaptin5 FXXPhi-type motifs bind to the same or highly overlapping sites in the AP-1 gamma-ear. This binding is modulated by residues adjacent to the core motifs.
Mesh Terms:
ADP-Ribosylation Factors, Adaptor Proteins, Vesicular Transport, Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Binding, Competitive, Brain, COS Cells, Carrier Proteins, DNA, Complementary, Dose-Response Relationship, Drug, Escherichia coli, Gene Library, Glutathione Transferase, Humans, Immunoblotting, Membrane Proteins, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Peptides, Phenylalanine, Plasmids, Protein Binding, Protein Structure, Tertiary, Receptor, IGF Type 2, Sequence Homology, Amino Acid, Transcription Factor AP-1, Tryptophan, Vesicular Transport Proteins, trans-Golgi Network
ADP-Ribosylation Factors, Adaptor Proteins, Vesicular Transport, Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Binding, Competitive, Brain, COS Cells, Carrier Proteins, DNA, Complementary, Dose-Response Relationship, Drug, Escherichia coli, Gene Library, Glutathione Transferase, Humans, Immunoblotting, Membrane Proteins, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Peptides, Phenylalanine, Plasmids, Protein Binding, Protein Structure, Tertiary, Receptor, IGF Type 2, Sequence Homology, Amino Acid, Transcription Factor AP-1, Tryptophan, Vesicular Transport Proteins, trans-Golgi Network
J. Biol. Chem.
Date: Apr. 23, 2004
PubMed ID: 14973137
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