抑制SIRT1脱乙酶的蛋白-蛋白相互作用是通过翻译后修饰编排的
Troy C Krzysiak1, You-Jin Choi2,3, Yong Joon Kim1
1Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Protein science : a publication of the Protein Society
|March 27, 2024
概括
胰岛素通过DBC1和PACS-2控制日常SIRT1抑制,影响燃料代谢. 这条路径的路径.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- Sirtuin 1 (SIRT1) 活性对能量平衡至关重要,并与各种疾病有关.
- 胰岛素信号传递涉及DBC1 (在乳腺癌中被删除1) 和PACS-2 (酸氨酸聚分类蛋白2) 在调节SIRT1.
- 对SIRT1的日常调节对于新陈代谢适应食和禁食状态至关重要.
研究的目的:
- 阐明DBC1和PACS-2调节昼间SIRT1抑制的分子机制.
- 描述DBC1-SIRT1相互作用的结构基础及其通过翻译后修改的调节.
- 研究这种途径在胰岛素依赖的代谢切换中的作用及其与疾病的关联.
主要方法:
- 进行X射线晶体学,以确定与SIRT1.1结合的DBC1S1-类域的结构.
- 核磁共振 (NMR) 光谱学以表征SIRT1 N端区域与DBC1的相互作用.
- 在体外酶分析和细胞局部化研究以评估SIRT1活性和转位.
- 分析翻译后的修饰 (乙化和化) 以及它们对相互作用的影响.
主要成果:
- 这项研究介绍了与SIRT1相互作用的DBC1S1-类域的X射线结构,以及SIRT1N终端区域参与的SIRT1和NMR数据.
- 在K112的DBC1乙化抑制了相互作用,而在S162/S172 (由CK2和GSK3) 的SIRT1的胰岛素依赖酸化刺激了它.
- 这导致PACS-2-依赖性抑制核SIRT1活动及其细胞质转移.
结论:
- 肝脏DBC1/PACS-2协调SIRT1的白天抑制,这对胰岛素介导的燃料代谢转变至关重要.
- DBC1/PACS-2-SIRT1通路的失调与肥胖和非酒精性脂肪肝等代谢疾病有关.
- 了解这个调节轴为代谢障碍提供了潜在的治疗点.
关键词:
在 CK2 中使用.DBC1 DBC1 是一个这是GSK3的GSK3.这是NAFLD.这是一场PACS-2的比赛.一个SIRT1系统.通过乙化处理.胰岛素的信号传递方式肝脏代谢 肝脏代谢肥胖 肥胖 肥胖 肥胖 肥胖 肥胖 肥胖 肥胖后翻译修改后的修改.蛋白质蛋白质相互作用更多相关视频
12:11Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization
Published on: February 27, 2020
6.9K
08:12Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins
Published on: January 8, 2018
11.3K
相关概念视频
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
Protein Modifications in the RER
5.2K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.2K
Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
