对eIF2β与eIF5,eIF2B和5MP1的相互作用以及它们通过CK2的调节的分子基础
Paul A Wagner1, Meimei Song1, Paul Doran1
1Boston University Chobanian & Avedisian School of Medicine.
概括
这项研究揭示了关键蛋白质如何与真核转化启动因子2 (eIF2) 相互作用,以调节蛋白质合成. 这些相互作用涉及eIF2β K-box,对于翻译控制至关重要,并通过酸化调节.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 细胞转化启动因子2 (eIF2) 对于将Met-tRNAi输送到核糖体至关重要.
- eIF2β亚单元包含与调节蛋白相互作用的氨酸丰富的重复 (K-盒).
研究的目的:
- 阐明eIF2β与eIF5,eIF2B和5MP相互作用的分子基础和动态.
- 了解这些相互作用如何调节翻译启动.
主要方法:
- 在X射线晶体学.
- 核磁共振 (NMR) 光谱学 核磁共振 (NMR) 光谱学
主要成果:
- 对eIF5.5的K盒外的eIF2β上确定了一个扩展的结合位点.
- 证明eIF2β对eIF5,eIF2Bε和5MP1.1具有三个不同的结合位点.
- 显示的eIF2B加速了eIF5解离,而5MP1破坏了eIF5结合的稳定性,影响了开始的编码子选择.
结论:
- CK2的相仿性突变增强了结合亲缘关系,表明它在翻译装置的重塑和稳定方面发挥了作用.
- 这些发现提供了通过蛋白质-蛋白质相互作用和酸化对翻译启动的动态调节的见解.
相关概念视频
Positive Regulator Molecules
5.7K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.7K
MAPK Signaling Cascades
6.1K
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...
6.1K
M-Cdk Drives Transition Into Mitosis
5.7K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
Inhibition of Cdk Activity
4.9K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
cAMP-dependent Protein Kinase Pathways
6.6K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.6K
PI3K/mTOR/AKT Signaling Pathway
4.0K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
4.0K


