Protein prenylation is essential for many cellular processes including signal transduction, cytoskeletal reorganization, and membrane trafficking. Here, we identify a novel type of protein prenyltransferase, which we named geranylgeranyltransferase type-III (GGTase-III). GGTase-III consists of prenyltransferase alpha subunit repeat containing 1 (PTAR1) and the β subunit of RabGGTase. Using a biotinylated geranylgeranyl analogue, we identified the Golgi SNARE protein Ykt6 as a substrate of GGTase-III. GGTase-III transfers a geranylgeranyl group to mono-farnesylated Ykt6, generating doubly prenylated Ykt6. The crystal structure of GGTase-III in complex with Ykt6 provides structural basis for Ykt6 double prenylation. In GGTase-III-deficient cells, Ykt6 remained in a singly prenylated form, and the Golgi SNARE complex assembly was severely impaired. Consequently, the Golgi apparatus was structurally disorganized, and intra-Golgi protein trafficking was delayed. Our findings reveal a fourth type of protein prenyltransferase that generates geranylgeranyl-farnesyl Ykt6. Double prenylation of Ykt6 is essential for the structural and functional organization of the Golgi apparatus.

中文翻译：

---

SNARE香叶基香叶基转移酶，对高尔基体的组织必不可少。

蛋白质异戊二烯化对于许多细胞过程至关重要，包括信号转导，细胞骨架重组和膜运输。在这里，我们确定了一种新型的蛋白质异戊二烯基转移酶，我们将其命名为III型香叶基香叶基转移酶（GGTase-III）。GGTase-III由异戊二烯基转移酶α亚基重复序列（含1（PTAR1）和RabGGTase的β亚基）组成。使用生物素化的香叶基香叶基类似物，我们确定了高尔基网罗蛋白质Ykt6作为GGTase-III的底物。GGTase-III将香叶基香叶基转移至单法呢基化的Ykt6，生成双烯丙基化的Ykt6。与Ykt6结合的GGTase-III的晶体结构为Ykt6双炔基化提供了结构基础。在GGTase-III缺陷型细胞中，Ykt6保留为单一的异戊二烯化形式，并且高尔基SNARE复合体装配严重受损。因此，高尔基体结构混乱，高尔基体内蛋白运输被延迟。我们的发现揭示了第四种类型的蛋白质异戊二烯基转移酶，其产生香叶基香叶基-法呢基Ykt6。Ykt6的双烯丙基化对于高尔基体的结构和功能组织至关重要。