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.
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, Cyclic Nucleotide Phosphodiesterases, Type 6, GTP-Binding Proteins, Guanine Nucleotide Dissociation Inhibitors, Guanosine Triphosphate, Humans, Macromolecular Substances, Mice, Models, Molecular, Molecular Sequence Data, Phosphoric Diester Hydrolases, Protein Structure, Tertiary, Structure-Activity Relationship, rho GTP-Binding Proteins
Amino Acid Sequence, Animals, Binding Sites, Cyclic Nucleotide Phosphodiesterases, Type 6, GTP-Binding Proteins, Guanine Nucleotide Dissociation Inhibitors, Guanosine Triphosphate, Humans, Macromolecular Substances, Mice, Models, Molecular, Molecular Sequence Data, Phosphoric Diester Hydrolases, Protein Structure, Tertiary, Structure-Activity Relationship, rho GTP-Binding Proteins
EMBO J.
Date: May. 01, 2002
PubMed ID: 11980706
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