多系统蛋白质病变与VCP相互作用的小蛋白质之间的脂肪联系
Firyal Ramzan1, Ashish Kumar1, Fatima Abrar1
1Department of Biology, University of Waterloo, Waterloo, ON, Canada.
Cell death discovery
|August 8, 2024
概括
小VCP相互作用蛋白 (SVIP) 化对于多系统蛋白质病变 (MSP) 中的细胞死亡至关重要. 阻止SVIP基化可以防止细胞毒性,这表明SVIP基化是MSP的潜在治疗标.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 多系统蛋白质病变 (MSP) 是一种罕见的,主导性遗传性疾病,由含瓦洛蛋白 (VCP) 基因的突变引起.
- MSP包括前性痴呆症,包容性身体肌肉病,帕杰特骨疾病和肌缩侧面硬化症,患者表现各不相同.
- VCP的多样化的细胞功能由50多个辅助因子调节,包括小VCP相互作用蛋白 (SVIP).
研究的目的:
- 调查SVIP在MSP中VCP介导的细胞功能障碍中的作用.
- 为了确定SVIP化是否影响VCP局部化和细胞毒性.
主要方法:
- 研究了SVIP在VCP局部化到 lysosomes中的作用.
- 已经证明了SVIP的myristoylation和palmitoylation.
- 评估了SVIP化对在存在VCP变体时细胞死亡的影响.
主要成果:
- SVIP以一种依赖于化的方式将VCP引导到 lysosomes.
- 在SVIP中,Glycine 2进行了myristoylation,Cysteine 4和7进行了palmitoylation. 在SVIP中,Glycine 2进行了myristoylation,Cysteine 4和7进行了palmitoylation.
- 对于MSP相关R155H-VCP变体诱导的细胞死亡,需要SVIP化;阻断myristoylation可以防止这种毒性.
结论:
- 在MSP中,SVIP化是与VCP相关的细胞毒性的关键调解者.
- 针对SVIP化,特别是myristoylation,可能为MSP提供一种新的治疗策略.
更多相关视频
00:07Quantification of Protein Interaction Network Dynamics using Multiplexed Co-Immunoprecipitation
Published on: August 21, 2019
8.3K
10:01Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies
Published on: November 28, 2017
19.6K
相关概念视频
Protein Complexes with Interchangeable Parts
2.5K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.5K
Protein Complex Assembly
10.6K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.6K
Protein-protein Interfaces
12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K
Intralumenal Vesicles and Multivesicular Bodies
3.4K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.4K
Protein Networks
3.9K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
3.9K
Covalently Linked Protein Regulators
1.6K
1.6K
