相关实验视频
Updated: May 29, 2026

09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
在相互连接的多蛋白质复合体内,N终端乙化作为慕增强剂
Daniel C Scott1, Julie K Monda, Eric J Bennett
1Structural Biology Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
概括
Ubc12酶的N端乙化指导蛋白质相互作用,并促进库林化. 这项研究揭示了N端乙化如何引导Ubc12的过程.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 许多真核蛋白经历N端乙化,但其在调解蛋白相互作用中的作用尚不清楚.
- E2酶Ubc12和E3酶Dcn1是化途径的关键组成部分,该途径修改了Cul1蛋白.
研究的目的:
- 阐明Ubc12的N端乙化影响其与E3结合酶相互作用的结构机制.
- 定义N端乙化在Nedd8到Cul1.1的E3依赖性结合中所起的作用.
主要方法:
- 该研究采用了结构,生化,生物物理和遗传分析.
- 关键技术包括X射线结晶学,酶活性测定和突变研究.
主要成果:
- Ubc12的N端乙化决定了它通过E3结合酶Dcn1.1通过Cul1的特定结合.
- 结构分析显示,Ubc12的N-乙甲因被埋在Dcn1的疏水口袋中,从而促进了库林缩.
- 乙化指导Ubc12-Dcn1相互作用,并防止N端电荷排斥.
结论:
- 这项研究确立了N-终端乙化和类似于ubiquitin的蛋白质结合之间的直接联系.
- 定义了N端乙化依赖蛋白质识别的新机制,突出了其在调节蛋白质相互作用和细胞过程中的重要性.
相关概念视频
Phase II Reactions: Acetylation Reactions
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
Covalently Linked Protein Regulators
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.
Cholinergic Neurons: Neurotransmission
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Catenins
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Tail-anchoring of Proteins in the ER Membrane
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...

