Structural basis for Arl1-dependent targeting of homodimeric GRIP domains to the Golgi apparatus

Golgins are large coiled-coil proteins that play a role in Golgi structure and vesicle traffic. The Arf-like GTPase ArI1 regulates the translocation of GRIP domain-containing golgins to Golgi membranes. We report here the 1.7 Angstrom resolution structure of human ArI1-GTP in a complex with the GRIP domain of golgin-245. The structure reveals that the GRIP domain consists of an S-shaped arrangement of three helices. The domain forms a homodimer that binds two ArI1-GTPs using two helices from each monomer. The structure is consistent with golgin-245 forming parallel coiled-coils and suggests how ArI1-GTP/GRIP complexes interact with Golgi membranes via the N termini of ArI1-GTP and the C-terminal tails of the GRIP domains. In cells, bivalent association with ArI1-GTP would increase residence time of the golgins on Golgi membranes. Despite no conservation of sequence, topology, or even helical direction, several other effectors form similar interactions with small GTPases via a pair of alpha helices, suggesting a common structural basis for effector recognition.