在非典型的RanGTP•Kap114•H2A-H2B复合体中,RanGTP启动H2A-H2B从Kap114释放的机制
Jenny Jiou1, Joy M Shaffer2, Natalia E Bernades1
1Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
概括
核导入受体Importin-9及其同类Kap114同时结合素H2A-H2B和RanGTP. 冷-EM结构揭示了这个复合体如何促进H2A-H2B释放以进行核细胞组装.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 进口因-9促进了核中组织素H2A-H2B的运输.
- RanGTP通常将货物与进口素分离,但稳定地结合进口素-9•H2A-H2B复合体.
- 同时绑定和释放货物的机制仍然不清楚.
研究的目的:
- 阐明H2A-H2B和RanGTP与Importin-9同源Kap114.4同时结合的结构基础.
- 了解三元复合体如何定位H2A-H2B进行释放和核细胞组合.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定结构.
- 解决了Kap114•RanGTP,Kap114•H2A-H2B,以及RanGTP•Kap114•H2A-H2B复合体的结构.
- 保存的Kap114与货物和GTPase的相互作用的结构分析.
主要成果:
- 化EM结构揭示了Kap114如何同时结合H2A-H2B和RanGTP.
- 兰GTP与Kap114的N端重复结合,而H2A-H2B通过其酸性补丁与C端重复结合.
- 在三元复合体中,RanGTP诱导了Kap114的结构变化,释放了H2A-H2B对接域.
结论:
- 卡普114的保存结构使其能够同时结合素H2A-H2B和RanGTP.
- RanGTP与Kap114的H2A-H2B位置结合,以便有效地转移到核细胞体.
- 这种机制对于核进口和核组装至关重要.
相关概念视频
Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
MAPK Signaling Cascades
5.7K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K
Transcription Initiation
16.5K
Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
The promoters and enhancers and their accessory proteins allow tight regulation of...
16.5K
RNA Polymerase II Accessory Proteins
9.3K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.3K
Homologous Recombination
50.7K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.7K
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


