Cryo-EM structure and biochemical analysis reveal the basis of the   functional difference between human PI3KC3-C1 and-C2

doi:10.1038/cr.2017.94

CORC > 北京大学 > 生命科学学院

	Cryo-EM structure and biochemical analysis reveal the basis of the functional difference between human PI3KC3-C1 and-C2
	Ma, Meisheng ; Liu, Jun-Jie ; Li, Yan ; Huang, Yuwei ; Ta, Na ; Chen, Yang ; Fu, Hua ; Ye, Ming-Da ; Ding, Yuehe ; Huang, Weijiao ; Wang, Jia ; Dong, Meng-Qiu ; Yu, Li ; Wang, Hong-Wei
刊名	CELL RESEARCH
	2017
关键词	PI3KC3 ATG14L UVRAG autophagy PI cryo-EM PHOSPHATIDYLINOSITOL 3-KINASE COMPLEXES BECLIN 1 ELECTRON-MICROSCOPY SACCHAROMYCES-CEREVISIAE AUTOPHAGOSOME FORMATION ENDOPLASMIC-RETICULUM MOLECULAR-DYNAMICS UVRAG SYSTEM YEAST
DOI	10.1038/cr.2017.94
英文摘要	Phosphatidylinositol 3-phosphate (PI3P) plays essential roles in vesicular trafficking, organelle biogenesis and autophagy. Two class III phosphatidylinositol 3-kinase (PI3KC3) complexes have been identified in mammals, the AT-G14L complex (PI3KC3-C1) and the UVRAG complex (PI3KC3-C2). PI3KC3-C1 is crucial for autophagosome biogenesis, and PI3KC3-C2 is involved in various membrane trafficking events. Here we report the cryo-EM structures of human PI3KC3-C1 and PI3KC3-C2 at sub-nanometer resolution. The two structures share a common L-shaped overall architecture with distinct features. EM examination revealed that PI3KC3-C1 "stands up" on lipid monolayers, with the ATG14L BATs domain and the VPS34 C-terminal domain (CTD) directly contacting the membrane. Biochemical dissection indicated that the ATG14L BATs domain is responsible for membrane anchoring, whereas the CTD of VPS34 determines the orientation. Furthermore, PI3KC3-C2 binds much more weakly than PI3KC3-C1 to both PI-containing liposomes and purified endoplasmic reticulum (ER) vesicles, a property that is specifically determined by the ATG14L BATs domain. The in vivo ER localization analysis indicated that the BATs domain was required for ER localization of PI3KC3. We propose that the different lipid binding capacity is the key factor that differentiates the functions of PI3KC3-C1 and PI3KC3-C2 in autophagy.; Ministry of Science and Technology of China [2016YFA0500202, 2016YFA0501100]; National Natural Science Foundation of China [31430053, 31621063]; Natural Science Foundation of China International Cooperation and Exchange Program [31561143002]; Beijing Municipal Science & Technology Commission [Z161100000116034]; Independent Research of Tsinghua University [20161080135]; SCI(E); ARTICLE; 8; 989-1001; 27
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/471820]
专题	生命科学学院
推荐引用方式 GB/T 7714	Ma, Meisheng,Liu, Jun-Jie,Li, Yan,et al. Cryo-EM structure and biochemical analysis reveal the basis of the functional difference between human PI3KC3-C1 and-C2[J]. CELL RESEARCH,2017.
APA	Ma, Meisheng.,Liu, Jun-Jie.,Li, Yan.,Huang, Yuwei.,Ta, Na.,...&Wang, Hong-Wei.(2017).Cryo-EM structure and biochemical analysis reveal the basis of the functional difference between human PI3KC3-C1 and-C2.CELL RESEARCH.
MLA	Ma, Meisheng,et al."Cryo-EM structure and biochemical analysis reveal the basis of the functional difference between human PI3KC3-C1 and-C2".CELL RESEARCH (2017).