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 Arl1 regulates the translocation of GRIP domain-containing golgins to Golgi membranes. We report here the 1.7 A resolution structure of human Arl1-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 Arl1-GTPs using two helices from each monomer. The structure is consistent with golgin-245 forming parallel coiled-coils and suggests how Arl1-GTP/GRIP complexes interact with Golgi membranes via the N termini of Arl1-GTP and the C-terminal tails of the GRIP domains. In cells, bivalent association with Arl1-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.
MRC Laboratory of Molecular Biology, MRC Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
Bojana
B
Panic
Olga
O
Perisic
Dmitry B
DB
Veprintsev
Roger L
RL
Williams
Sean
S
Munro
D020727:ADP-Ribosylation Factors; D000818:Animals; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism; D019556:COS Cells; D019281:Dimerization; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D001324:Autoantigens; C098772:GOLGA4 protein, human; D046911:Macromolecular Substances; D008565:Membrane Proteins; C097313:ADP-ribosylation factor related proteins; D020558:GTP Phosphohydrolases; D020727:ADP-Ribosylation Factors