核出口受体CRM1的晶体结构与Snurportin1和RanGTP复合在一起
Thomas Monecke1, Thomas Güttler, Piotr Neumann
1Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik, GZMB, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
概括
晶体结构揭示了CRM1蛋白如何识别各种货物,例如用于核出口的SPN1. 这一发现解释了CRM1的存在.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 细胞生物学 细胞生物学
背景情况:
- CRM1 (染色体区域维护1) 是一个关键的核出口受体.
- CRM1调解了许多蛋白质和RNA复合物的从核到细胞质的运输.
- CRM1识别其多样化的货物分子的机制在很大程度上仍然难以捉摸.
研究的目的:
- 阐明CRM1-货物识别的结构基础.
- 了解CRM1如何与snurportin1 (SPN1) 相互作用,SPN1是状体U snRNP的核导入适配器.
- 揭示RanGTP在CRM1中介的出口过程中的作用.
主要方法:
- 使用X射线结晶学来确定SPN1-CRM1-RanGTP复合物的结构.
- 进行了高分辨率 (2.5安格斯特罗姆) 的结构分析.
- 进行了对蛋白质-蛋白质相互作用和构造变化的详细分析.
主要成果:
- 该SPN1-CRM1-RanGTP出口复合物的晶体结构以2.5安格斯特罗姆分辨率确定.
- 确定了CRM1和SPN1之间的特定相互作用,包括疏水性对接和疏水性接触.
- 通过RanGTP结合,可以诱导CRM1的远程构造变化,从而促进货物结合.
结论:
- CRM1通过水性和水友性相互作用的组合来识别SPN1.
- 该结构为CRM1结合各种货物的能力提供了分子解释.
- 兰GTP在通过全调节促进货物与CRM1结合方面发挥着至关重要的作用.
相关概念视频
Nuclear Export
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...
Directionality of Nuclear Transport
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...
Nuclear Protein Sorting
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...
Nuclear Export of mRNA
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...
Nuclear Export of mRNA
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...
Nuclear Localization Signals and Import
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...
