The complex of Arl2-GTP and PDE delta: from structure to function.
Arf-like (Arl) proteins are close relatives of the Arf regulators of vesicular transport, but their function is unknown. Here, we present the crystal structure of full-length Arl2-GTP in complex with its effector PDE delta solved in two crystal forms (Protein Data Bank codes 1KSG, 1KSH and 1KSJ). Arl2 shows a dramatic conformational change from the GDP-bound form, which suggests that it is reversibly membrane associated. PDE delta is structurally closely related to RhoGDI and contains a deep empty hydrophobic pocket. Further experiments show that H-Ras, Rheb, Rho6 and G alpha(i1) interact with PDE delta and that, at least for H-Ras, the intact C-terminus is required. We suggest PDE delta to be a specific soluble transport factor for certain prenylated proteins and Arl2-GTP a regulator of PDE delta-mediated transport.
Hanzal-Bayer
Michael
M
Max-Planck-Institut für molekulare Physiologie, Abteilung Strukturelle Biologie, Otto-Hahn-Strasse 11, D-44227 Dortmund, Germany.
Renault
Louis
L
Roversi
Pietro
P
Wittinghofer
Alfred
A
Hillig
Roman C
RC
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000502:physiology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
C569638:ARHGDIA protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D046911:Macromolecular Substances; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D006160:Guanosine Triphosphate; D010727:Phosphoric Diester Hydrolases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517431:PDE6B protein, human; C517438:Pde6b protein, mouse; C410130:ARL2 protein, human; C485819:Arl2 protein, mouse; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins