Structure and mechanism of human diacylglycerol O-acyltransferase 1

	Structure and mechanism of human diacylglycerol O-acyltransferase 1
	Wang, L; Qian, HW; Nian, Y; Han, YM; Ren, ZN; Zhang, HZ; Hu, LY; Prasad, BVV; Laganowsky, A; Yan, N; Zhou, M
	2020
发表期刊	NATURE
ISSN	0028-0836
卷号	581 期号:7808 页码:329-+
摘要	The structure of human diacylglycerol O-acyltransferase 1, a membrane protein that synthesizes triacylglycerides, is solved with cryo-electron microscopy, providing insight into its function and mechanism of enzymatic activity. Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans(1). DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins(2,3). How human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions is unknown. The absence of three-dimensional structures also hampers rational targeting of DGAT1 for therapeutic purposes. Here we present the cryo-electron microscopy structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold that we name the MBOAT fold. The MBOAT fold in DGAT1 forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 can exist as either a homodimer or a homotetramer and the two forms have similar enzymatic activity. The N terminus of DGAT1 interacts with the neighbouring protomer and these interactions are required for enzymatic activity.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13791
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
推荐引用方式 GB/T 7714	Wang, L,Qian, HW,Nian, Y,et al. Structure and mechanism of human diacylglycerol O-acyltransferase 1[J]. NATURE,2020,581(7808):329-+.
APA	Wang, L.,Qian, HW.,Nian, Y.,Han, YM.,Ren, ZN.,...&Zhou, M.(2020).Structure and mechanism of human diacylglycerol O-acyltransferase 1.NATURE,581(7808),329-+.
MLA	Wang, L,et al."Structure and mechanism of human diacylglycerol O-acyltransferase 1".NATURE 581.7808(2020):329-+.

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