Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p

The GATE-16 protein participates in intra-Golgi transport and can associate with the N-ethylmaleimide-sensitive fusion protein and with Golgi SNAREs, The yeast ortholog of GATE-16 is the autophagocytosis factor Aut7p, GATE-16 is also closely related to the GABA receptor-associated protein (GABARAP), which has been proposed to cluster neurotransmitter receptors by mediating interaction with the cytoskeleton, and to the light chain-3 subunit of the neuronal microtubule-associated protein complex. Here, we present the crys tal structure of GATE-16 refined to 1.8 Angstrom resolution. GATE-16 contai ns a ubiquitin fold decorated by two additional N-terminal helices, Protein s with strong structural similarity but no detectable sequence homology to GATE-16 include Ras effectors that mediate diverse downstream functions, bu t each interacts with Ras by forming pseudo-continuous beta-sheets, The GAT E-16 surface suggests that it binds its targets in a similar manner. Moreov er, a second potential protein-protein interaction site on GATE-16 may expl ain the adapter activity observed for members of the GATE-16 family.