在histidine重复中,DNA刺激SIRT6转化为单ADP-ribosylate蛋白
bioRxiv : the preprint server for biology
|August 30, 2024
概括
赛尔图因6 (SIRT6) 酶使用NAD+修改蛋白质,作为一个histidine mono-ADP-ribosyltransferase. 它的活性是由双链DNA末端激活的,并向多胺通道.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 酶学 是一种酶学.
背景情况:
- 赛尔图因 (NAD+依赖的III类 lysine deacylases) 与衰老和疾病有关.
- 赛尔图因6 (SIRT6) 作为一个组 histone脱乙酶和单-ADP-ribosyltransferase 的功能.
- 由于基质和上下文知识有限,SIRT6的单-ADP-ribosylation (mARylation) 作用,特别是在DNA损伤反应中,尚不清楚.
研究的目的:
- 为了研究SIRT6在复制系统中的mARylation活性.
- 为了确定SIRT6的mARylation功能的细胞背景和基质.
- 描述SIRT6的mARylation活动的酶机制和基质特异性.
主要方法:
- 使用了商业上可用的ADP-ribosylation检测试剂.
- 采用重新组建的系统来研究SIRT6活动.
- 生物化学试验用于识别基质基因.
主要成果:
- 通过结合双链DNA末端,SIRT6的mARylation活性被显著激活.
- 确定了一种SIRT6 mARylation的新型基质基因:多西丁 (polyHis) 重复通道.
- 在已知的SIRT6 mARylation基质和结合伙伴中存在多西丁通道.
结论:
- SIRT6作为一个胺单-ADP-ribosyltransferase的功能,与其氨酸脱酶活性不同.
- DNA 损伤,特别是 dsDNA 末端,是 SIRT6 的 mARylation 功能的关键激活剂.
- 鉴定多西丁通道作为标动机,为SIRT6的酶作用和基质识别提供了关键的见解.
更多相关视频
07:26Site Specific Lysine Acetylation of Histones for Nucleosome Reconstitution using Genetic Code Expansion in Escherichia coli
Published on: December 26, 2020
4.0K
08:33Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models
Published on: March 24, 2019
7.5K
相关概念视频
Histone Modification
13.2K
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...
13.2K
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
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
Protein Modifications in the RER
5.1K
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...
5.1K
Riboswitches
8.1K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.1K
The Nucleosome Core Particle
895
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
895
