A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus.

The EMBO journal 2020 Apr 15

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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. © 2020 The Authors.

Citation

Ryutaro Shirakawa, Sakurako Goto-Ito, Kota Goto, Shonosuke Wakayama, Haremaru Kubo, Natsumi Sakata, Duc Anh Trinh, Atsushi Yamagata, Yusuke Sato, Hiroshi Masumoto, Jinglei Cheng, Toyoshi Fujimoto, Shuya Fukai, Hisanori Horiuchi. A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus. The EMBO journal. 2020 Apr 15;39(8):e104120