Qureshi Bilal M, Schmidt Andrea, Behrmann Elmar, Bürger Jörg, Mielke Thorsten, Spahn Christian M T, Heck Martin, Scheerer Patrick
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, D-10117, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Institut für Medizinische Physik und Biophysik (CC2), Group Protein X-ray Crystallography and Signal Transduction, Charitéplatz 1, D-10117, Berlin, Germany.
Nat Commun. 2018 Jan 8;9(1):90. doi: 10.1038/s41467-017-02569-y.
Isoprenylated proteins are associated with membranes and their inter-compartmental distribution is regulated by solubilization factors, which incorporate lipid moieties in hydrophobic cavities and thereby facilitate free diffusion during trafficking. Here we report the crystal structure of a solubilization factor, the prenyl-binding protein (PrBP/δ), at 1.81 Å resolution in its ligand-free apo-form. Apo-PrBP/δ harbors a preshaped, deep hydrophobic cavity, capacitating apo-PrBP/δ to readily bind its prenylated cargo. To investigate the molecular mechanism of cargo solubilization we analyzed the PrBP/δ-induced membrane dissociation of rod photoreceptor phosphodiesterase (PDE6). The results suggest that PrBP/δ exclusively interacts with the soluble fraction of PDE6. Depletion of soluble species in turn leads to dissociation of membrane-bound PDE6, as both are in equilibrium. This "solubilization by depletion" mechanism of PrBP/δ differs from the extraction of prenylated proteins by the similar folded solubilization factor RhoGDI, which interacts with membrane bound cargo via an N-terminal structural element lacking in PrBP/δ.
异戊二烯化蛋白与膜相关，其在不同区室间的分布受增溶因子调节，这些增溶因子将脂质部分纳入疏水腔，从而在运输过程中促进自由扩散。在此，我们报道了一种增溶因子——异戊二烯结合蛋白（PrBP/δ）在无配体的脱辅基形式下1.81Å分辨率的晶体结构。脱辅基PrBP/δ具有一个预成型的深疏水腔，使脱辅基PrBP/δ能够轻易结合其异戊二烯化的货物。为了研究货物增溶的分子机制，我们分析了PrBP/δ诱导的视杆光感受器磷酸二酯酶（PDE6）的膜解离。结果表明，PrBP/δ仅与PDE6的可溶部分相互作用。可溶性物质的耗尽进而导致膜结合的PDE6解离，因为两者处于平衡状态。PrBP/δ的这种“通过耗尽实现增溶”机制不同于由结构相似的增溶因子RhoGDI对异戊二烯化蛋白的提取，RhoGDI通过PrBP/δ中缺乏的N端结构元件与膜结合货物相互作用。
