模拟人类线粒体ADP/ATP载体的不同构造,使用AlphaFold和蛋白质-连接体复合体的分子动力学模拟
Virginia Quadrotta1, Fabio Polticelli1,2
1Department of Sciences, University of Roma Tre, Rome, Italy.
Computational and structural biotechnology journal
|April 14, 2025
概括
AlphaFold3和AlphaFold2准确地建模了ADP/ATP载体 (AAC),这是一个关键的线粒体蛋白质. 科拉布 折叠
科学领域:
- 结构生物学是结构生物学.
- 计算生物学是一种计算生物学.
- 生物化学 生物化学
背景情况:
- ADP/ATP载体 (AAC) 是一个关键的线粒体蛋白调节细胞能量.
- AAC属于溶性载体家族25 (SLC25) 组,与癌症等疾病有关.
- AAC通过交替访问机制运行,在细胞质 (c状态) 和线粒体 (m状态) 结构之间切换.
研究的目的:
- 评估AlphaFold2 (AF2) 和AlphaFold3 (AF3) 用于模拟SLC25家族蛋白质,特别是人类AAC.
- 将AF3的蛋白质连接体复合体预测与传统的建模和对接方法进行比较.
- 研究AAC的基质结合,稳定以及突变对其功能的影响.
主要方法:
- 利用AlphaFold2和AlphaFold3进行人类AAC的结构建模.
- 员工 ColabFold AF2 的实现,用于 *ab initio* m-state 建模.
- 集成分子动力学 (MD) 模拟与AF3预测复合体.
主要成果:
- AF2和AF3都显示出对AAC的c状态构造的偏差.
- ColabFold成功生成了人类AAC的第一个*ab initio*m-state模型.
- 模拟MD提供了关于基质结合,稳定和突变对AAC动态的影响的见解.
- AF3显示了在c状态中建模蛋白-联结体相互作用的潜力.
结论:
- 当对实验数据进行验证时,AlphaFold模型是可靠的.
- AF3对蛋白质 - 连接体相互作用研究有希望,特别是对于像AAC.这样的膜蛋白.
- 这项研究增强了对AAC机制的理解,以及人工智能工具在结构生物学中的实用性.
- 这些发现支持使用AlphaFold来研究溶解物载体和膜蛋白.
相关概念视频
The ADP/ATP Carrier Protein
3.1K
ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
3.1K
Chemiosmosis
96.3K
Oxidative phosphorylation is a highly efficient process that generates large amounts of adenosine triphosphate (ATP), the basic unit of energy that drives many cellular processes. Oxidative phosphorylation involves two processes— the electron transport chain and chemiosmosis.
Electron Transport Chain
The electron transport chain involves a series of protein complexes on the inner mitochondrial membrane that undergo a series of redox reactions. At the end of this chain, the electrons...
Electron Transport Chain
The electron transport chain involves a series of protein complexes on the inner mitochondrial membrane that undergo a series of redox reactions. At the end of this chain, the electrons...
96.3K
ATP Synthase: Mechanism
13.7K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
13.7K
Energy to Drive Translocation
2.0K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.0K
Structure of Porins
2.8K
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...
2.8K
The Inner Mitochondrial Membrane
3.2K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.2K


