Zhang Houbin, Constantine Ryan, Frederick Jeanne M, Baehr Wolfgang
Department of Ophthalmology, John A. Moran Eye Center, University of Utah Health Science Center, 65 Mario Capecchi Dr., Salt Lake City, UT 84132, USA.
Vision Res. 2012 Dec 15;75:19-25. doi: 10.1016/j.visres.2012.08.013. Epub 2012 Aug 29.
Expressed ubiquitously, PrBP/δ functions as chaperone/co-factor in the transport of a subset of prenylated proteins. PrBP/δ features an immunoglobulin-like β-sandwich fold for lipid binding, and interacts with diverse partners. PrBP/δ binds both C-terminal C15 and C20 prenyl side chains of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras superfamily. PrBP/δ also interacts with the small GTPases, ARL2 and ARL3, which act as release factors (GDFs) for prenylated cargo. Targeted deletion of the mouse Pde6d gene encoding PrBP/δ resulted in impeded trafficking to the outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and geranylgeranylated, respectively. Rod and cone transducin trafficking was largely unaffected. These trafficking defects produce progressive cone-rod dystrophy in the Pde6d(-/-) mouse.
PrBP/δ在全身广泛表达,在一组异戊二烯化蛋白的转运过程中作为伴侣蛋白/辅助因子发挥作用。PrBP/δ具有用于脂质结合的免疫球蛋白样β-折叠结构,并与多种蛋白相互作用。PrBP/δ既能结合光转导多肽的C末端C15和C20异戊二烯侧链,也能结合Ras超家族的小GTP结合(G)蛋白。PrBP/δ还与小GTP酶ARL2和ARL3相互作用,这两种酶作为异戊二烯化货物的释放因子(GDF)。对编码PrBP/δ的小鼠Pde6d基因进行靶向缺失,导致预计分别被法尼基化和香叶基香叶基化的GRK1和视锥细胞PDE6向视杆细胞外段的转运受阻。视杆细胞和视锥细胞转导素的转运在很大程度上未受影响。这些转运缺陷在Pde6d(-/-)小鼠中导致进行性视锥-视杆营养不良。