超越MitoCarta-扩大涉及线粒体功能的候选蛋白质列表,使用生物网络方法
Dmitriy Leyfer1,2, Jessica L Fetterman3
1Translational Sciences Department, Mitobridge, division of Astellas, Cambridge, MA 02138, USA.
NAR genomics and bioinformatics
|September 24, 2024
概括
研究人员扩展了线粒体蛋白质目录MitoCarta,通过识别2059个新的线粒体近位 (MitoProximal) 蛋白质. 这份全面的基因列表有助于诊断线粒体疾病和开发新疗法.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 线粒体疾病源于影响线粒体功能的遗传变异.
- 完整的线粒体基因列表对于诊断这些疾病和开发向疗法至关重要.
- MitoCarta是一个现有的实验识别的线粒体蛋白质目录.
研究的目的:
- 通过识别具有关键线粒体功能的蛋白质来扩展MitoCarta目录,即便它们并不严格局限于线粒体.
- 创建一个更全面的资源,以了解线粒体生物学和疾病.
主要方法:
- 利用一种计算方法,将STRING数据库基因网络数据与MitoCarta蛋白质集成在一起.
- 应用了严格的统计意义值来识别新的线粒体蛋白质.
- 通过确认氧化酸化复合体子单元和与疾病相关的基因的识别,验证了方法.
主要成果:
- 鉴定了2059个以前未在MitoCarta.中发现的线粒体近位 (MitoProximal) 蛋白质.
- 扩展名单包括所有氧化酸化复合体子单元和90%具有已知的氧化酸化疾病变异的基因.
- 发现了134种定位在线粒体中的蛋白质,但在MitoCarta 3.0.0中没有.
结论:
- 这项研究显著扩大了已知的线粒体基因组,几乎使MitoCarta的规模增加了三倍.
- 新的MitoProximal蛋白质清单是诊断线粒体和代谢疾病的宝贵资源.
- 这种增强的目录将加快病原体变体的识别和新疗法策略的开发.
相关概念视频
Mitochondrial Protein Sorting
4.3K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.3K
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
Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
Mitochondrial Precursor Proteins
2.5K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
2.5K
Porin Insertion in the Outer Mitochondrial Membrane
2.9K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
2.9K
Structure of Porins
2.9K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
2.9K


