The complex of Arl2-GTP and PDEδ: 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 PDEδ 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. PDEδ is structurally closely related to RhoGDI and contains a deep empty hydrophobic pocket. Further experiments show that H-Ras, Rheb, Rho6 and Gα(i1) interact with PDEδ and that, at least for H-Ras, the intact C-terminus is required. We suggest PDEδ to be a specific soluble transport factor for certain prenylated proteins and Arl2-GTP a regulator of PDEδ-mediated transport.