在H/ACAsnoRNP中进行的protomer间通信和功能不对称
Hemendra Singh Panwar1, Timothy J Vos2, Xiaoyan Xie1
1Department of Structural Biology, Van Andel Institute, Grand Rapids, MI 49503.
对于RNA的修饰和稳定性而言,H/ACA小核核核核核核蛋白蛋白 (H/ACA snoRNP) 是至关重要的. 这项研究揭示了它们的结构,解释了为什么两根毛RNA是常见的,以及突变如何导致疾病.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 遗传学 是一个
背景情况:
- H/ACA小核核核核核核蛋白蛋白 (H/ACA snoRNP) 对于细胞过程至关重要,包括RNA修饰,折叠和稳定性.
- 遗传性硬化症 (DC) 是一种罕见的遗传性疾病,与H/ACA蛋白的突变有关,影响核糖体生物发生和端粒维护.
研究的目的:
- 使用冷电子显微镜 (cryo-EM) 阐明H/ACAsnoRNP功能的结构基础.
- 了解伪尿活动的协调和特定蛋白质-RNA相互作用的作用.
- 为了研究与先天性硬化症相关的突变如何影响H/ACAsnoRNP功能.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定内生昆虫H/ACAsnoRNPs的结构.
- 生物化学和结构分析以表征蛋白质-蛋白质和蛋白质-RNA相互作用.
- 突变分析,以评估DC相关突变对伪尿素形成的影响.
主要成果:
- 多个冷-EM结构揭示了内生昆虫H/ACAsnoRNP与两个原体在一个两个头发针snoRNA.
- 描述了关键的相互作用,解释了两根针头结构的普遍性和协调伪尿化活动.
- 发现与DC相关的H/ACA蛋白的突变会损害伪尿素的形成,影响RNA修饰和核糖体生物发生.
- 在Nop10,Nhp2和Cbf5中的协调结构变化表明H/ACAsnoRNP活动的监管机制.
结论:
- 这项研究提供了详细的结构洞察,对RNA修饰有能力的H/ACAsnoRNP.
- 这些发现澄清了H/ACAsnoRNP功能在重要细胞过程中的结构基础.
- 这项工作将特定的H/ACAsnoRNP结构特征和突变与诸如先天性硬化症等疾病联系起来.
更多相关视频
07:08Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
07:26High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
Published on: July 18, 2017
相关概念视频
Protein Complexes with Interchangeable Parts
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Stereoisomerism
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
Membrane Asymmetry Regulating Transporters
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
