科学家们将产生甘油三酯的一种关键酶的结构形象化

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Scientists visualize the structure of a key enzyme that makes triglycerides

The finding may help to better understand heart disease, obesity and diabetes

这一发现可能有助于更好地了解心脏病、肥胖症和糖尿病

Date: 日期:March 11, 2020 2020年3月11日Source: 来源:Stony Brook University 石溪大学Summary: 摘要:The first structure of a lipin enzyme, which carries out an important step in the production of triglycerides, the main reservoir for long-term energy storage, will help scientists to better understand how lipins regulate the production of triglycerides. 一种脂肪酶的第一个结构,将帮助科学家更好地理解脂肪酶如何调节甘油三酯的生产。脂肪酶是长期储存能量的主要储存库,在生产甘油三酯过程中起着重要作用Share: 分享:    FULL STORY 完整故事


The first structure of a lipin enzyme, which carries out an important step in the production of triglycerides, the main reservoir for long-term energy storage, will help scientists to better understand how lipins regulate the production of triglycerides. Led by Mike Airola, PhD, of the Department of Biochemistry and Cell Biology in the College of Arts and Sciences and Renaissance School of Medicine at Stony Brook University, the structure also provides scientists with insights as to why mutations in the enzyme cause a loss of activity that leads to abnormal production of triglycerides implicated in heart disease, obesity and diabetes. The study will published in Nature Communications.

一种脂肪酶的第一个结构,将帮助科学家更好地理解脂肪酶如何调节甘油三酯的生产。脂肪酶是长期储存能量的主要储存库,在生产甘油三酯过程中起着重要作用。由石溪大学生物化学与细胞生物学系和文艺复兴医学院的 Mike Airola 博士领导,这个结构也为科学家提供了深刻的见解,为什么酶的突变会导致活性的丧失,从而导致与心脏病、肥胖症和糖尿病有关的甘油三酯的异常产生。这项研究将发表在《自然通讯》上。

Lipins complete the second to last step of triglyceride production. But when mutations interrupt lipin functions, the body loses its ability to store fat properly, thus potentially triggering a wide variety of metabolic-related conditions. Scientists have unsuccessfully tried to create the first visual structure a lipin enzyme since these enzymes were identified in 2001. Now Airola and colleagues successfully explain in the paper their first crystal structure of a specific enzyme called lipin PAP.

利平完成甘油三酯生产的倒数第二步。但是,当突变中断脂肪蛋白功能时,身体就失去了正常储存脂肪的能力,从而可能引发各种各样的代谢相关疾病。自从2001年这些酶被鉴定以来,科学家们一直没有成功地尝试创造出第一个视觉结构——脂肪酶。现在,Airola 和他的同事们成功地在论文中解释了他们的第一个特定酶的晶体结构,这种酶叫做 lipin PAP。

“This structure answers a long-standing question for how two essential regions, N-lip and C-lip, which are located on opposite ends of this protein in humans, come together to form a function enzyme to help make triglycerides,” explains Airola, Assistant Professor in the Department of Biochemistry & Cell Biology and director of the Airola Lab. “Using this structure also helps us understand how the protein interacts with membranes, which is key to regulating its activity and the production of triglycerides.”

生物化学与细胞生物学系助理教授兼 Airola 实验室主任 Airola 解释说: “这种结构回答了一个长期存在的问题,即人体内位于这种蛋白质两端的 N-lip 和 C-lip 这两个基本区域是如何聚集在一起形成一种功能酶来帮助制造甘油三酯的。”。“使用这种结构还有助于我们了解蛋白质如何与膜相互作用,这是调节其活性和生产甘油三酯的关键。”

The team used X-ray crystallography, mass spectrometry and biochemistry to visualize the structure, which represents the active state of a lipin enzyme during the production of triglycerides, as well as its other functions namely lipoprotein assembly and cellular signaling.

研究小组利用 X光散射技术、质谱法和生物化学的方法来观察脂肪酶的结构,这种结构代表了脂肪酶在产生甘油三酯过程中的活跃状态,以及它的其他功能,即脂蛋白组装和细胞信号传导。

Valerie Khayyo, a Stony Brook graduate student in the Biochemistry & Structural Biology Program and first author of the study, added that the structure enables researchers to understand and see specific mutational changes in the amino acid building blocks of lipins that result in disease.

该研究的第一作者、生物化学与结构生物学项目的斯托尼布鲁克研究生瓦莱丽 · 海约补充说,这种结构使研究人员能够理解并观察到脂肪蛋白的氨基酸组成部分中导致疾病的特定突变。

Khayyo noted that mutations in lipins are increasingly being identified in patients with muscle disorders as well, such as statin-induced myopathy and extreme cases in childhood rhabdomyolysis.

Khayyo 指出,脂质突变也越来越多地在肌肉疾病患者中被发现,例如他汀类药物引起的肌病和儿童横纹肌溶解症的极端病例。

Overall, Airola says that the structure and study consolidates many previous observations into a unifying framework and sets the stage for scientists to resolve several remaining important questions concerning how lipins are regulated.

总的来说,艾罗拉说,这个结构和研究将许多以前的观察结果合并成一个统一的框架,并为科学家解决几个关于如何管理脂肪的剩余的重要问题创造了条件。

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