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