Fig. 2

Prenyl-binding protein (PrBP/δ) crystal structures in various conformations. a Electrostatic surface representation of prenyl-binding protein (PrBP/δ) crystal structures. Electrostatic surface potentials were calculated using the program APBS with the non-linear Poisson–Boltzmann equation and contoured at ±5 kT e^{−1 78}. Negatively and positively charged surface areas are colored in red and blue, respectively. To elucidate the entrance of the cavity a yellow edge was introduced manually. The structured loop above the entrance in the PrBP/δ-Rheb-bound complex was removed in front for clarity. The cavity entrance of the three open conformations of PrBP/δ (PDB entries 5T4X, 3T5G, 4JHP) are more similar compared to the entry site of the displacement factor bound PrBP/δ in the closed conformation (PDB entry 1KSG). The apparent larger cavity entrance in 1KSG is a result of the increased flexibility in the flexible loop above the entrance. Moreover, the closure of the cavity results in an electrostatic surface potential rearrangement which may facilitate the release of the cargo. b Overall fold of PrBP/δ in cartoon representation with the hydrophobic cavity depicted as gray surface. The C15-farnesyl-moiety in the cargo-bound form is shown as yellow sticks. Binding partners of PrBP/δ are depicted in cartoon representation for clarifying the different additional protein interfaces in contrast to apo-PrBP/δ. c Close-up view of the PrBP/δ binding cavities. The PrBP/δ binding cavities are shown as ribbon representations and surfaces (gray). Key aromatic residues Phe65, Phe74, Phe94, Trp105, and Phe133, which define the bottom of the hydrophobic pockets for all selected crystal structure conformations, are depicted as stick representation. In particular, Phe94 and Trp105 of PrBP/δ indicate a rotation of their side chains after complex formation with the displacement factor (PDB entry 1KSG) and thereby a significant reduction of the cavity. Therefore, the PrBP/δ–Arl2 complex is incapable of incorporating any C15- or C20-isoprenyl-moieties