核孔复合体的粗粒模型中选择性和特异性的出现与无序FG-Nups的粗粒模型
Manoj K Patel1, Buddhapriya Chakrabarti2, Ajay S Panwar1
1Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. panwar@iitb.ac.in.
Physical chemistry chemical physics : PCCP
|November 29, 2023
概括
fenilalanine-glycine核素 (FG-Nups) 的疏水性决定了核孔综合体 (NPC) 的运输选择性和特异性. 最佳的货物运输发生在特定的FG-Nup疏水分数范围内,这对生物功能至关重要.
科学领域:
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
- 计算生物学 计算生物学
背景情况:
- 核孔复合体 (NPC) 调节核与细胞质之间的运输.
- 氨酸-甘氨酸核蛋白 (FG-Nups) 在NPC中形成了选择性屏障.
- 在货物运输中FG-Nup疏水性的作用仍然不完全理解.
研究的目的:
- 调查FG-Nup疏水性对整个NPC的接收器绑定货物运输的影响.
- 阐明NPC选择性和特异性背后的生物物理机制.
- 建立FG-Nup属性与它们的进化保护之间的联系.
主要方法:
- 使用Langevin动力学模拟与粗粒度,最小的NPC模型.
- 模拟FG-Nups作为疏水性-疏水性随机共聚物.
- 模拟的卡里奥菲林结合的受体-载荷复合体 (Kaps) 有或没有疏水域.
主要成果:
- 由于Kaps和FG-Nups之间的疏水相互作用,NPC选择性出现了.
- 在特定的FG-疏水分数范围 (0.05 ≤ f ≤ 0.20) 内观察到选择性,与生物学观察结果相匹配.
- 在NPC内部形成了一个类似水凝的网络,导致大小排除和在最佳范围内的增强转移.
结论:
- FG-Nup的疏水性是NPC运输选择性和特异性的关键决定因素.
- 这项研究为FG-Nup疏水分的进化保存提供了生物物理基础.
- 一种混合货物转移机制,将虚拟门和选择性相模型结合起来,在确定的最佳FG-水范围内运行.
相关概念视频
Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K
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
Nuclear Localization Signals and Import
5.7K
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
5.7K
Nuclear Export
3.7K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.7K
Directionality of Nuclear Transport
3.3K
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
3.3K
Nuclear Export of mRNA
7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K


