Molecular mechanism of membrane recruitment of GGA by ARF in lysosomal protein transport.

GGAs are critical for trafficking soluble proteins from the trans-Golgi network (TGN) to endosomes/lysosomes through interactions with TGN-sorting receptors, ADP-ribosylation factor (ARF) and clathrin. ARF-GTP bound to TGN membranes recruits its effector GGA by binding to the GAT domain, thus facilitating recognition of GGA for cargo-loaded receptors. Here we report ...
the X-ray crystal structures of the human GGA1-GAT domain and the complex between ARF1-GTP and the N-terminal region of the GAT domain. When unbound, the GAT domain forms an elongated bundle of three a-helices with a hydrophobic core. Structurally, this domain, combined with the preceding VHS domain, resembles CALM, an AP180 homolog involved in endocytosis. In the complex with ARF1-GTP, a helix-loop-helix of the N-terminal part of GGA1-GAT interacts with the switches 1 and 2 of ARF1 predominantly in a hydrophobic manner. These data reveal a molecular mechanism underlying membrane recruitment of adaptor proteins by ARF-GTP.
Mesh Terms:
ADP-Ribosylation Factor 1, ADP-Ribosylation Factors, Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Binding Sites, Carrier Proteins, Circular Dichroism, Cloning, Molecular, Crystallography, X-Ray, Guanosine Triphosphate, Humans, Kinetics, Lysosomes, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Protein Structure, Secondary, Protein Transport, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, trans-Golgi Network
Nat. Struct. Biol.
Date: May. 01, 2003
Download Curated Data For This Publication
137746
Switch View:
  • Interactions 1