小鼠CPEB3 PRD2结构域形成凝析物的结构顺序探索。

IF 3.9 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Faina Pinhero, Dhanya S. Reselammal, Arunima Sandeep, Parul Jain, Srinivasa M. Srinivasula and Vinesh Vijayan*, 
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引用次数: 0

摘要

哺乳动物长期记忆的维持需要由翻译调节蛋白CPEB3(细胞质聚腺苷化元件结合蛋白异构体3)的朊病毒样转化介导的可持续突触连接。CPEB3的n端朊病毒结构域由两个朊病毒亚结构域PRD1和PRD2组成,先前已被证明在赋予蛋白质朊病毒样特性方面发挥关键作用。我们已经报道了小鼠CPEB3的第一个朊病毒亚域(PRD1)的淀粉样蛋白核心。在此,我们在体外研究了小鼠PRD2 (mPRD2)的聚集特性和结构特征。我们发现mPRD2在非常低的浓度下发生相分离。有趣的是,mPRD2形成了稳定的淀粉样固体凝析物,而不是典型的液体凝析物。固体核磁共振和其他生物物理研究表明,mPRD2在凝析油中存在混合二级结构。我们提出,mPRD2独特的相分离行为可能是由于mPRD2氨基酸序列模式引起的构象变化,导致形成刚性的淀粉样自组装。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exploring the Structural Order of Condensates Formed by the PRD2 Domain of Mouse CPEB3

Exploring the Structural Order of Condensates Formed by the PRD2 Domain of Mouse CPEB3

The maintenance of long-term memory requires sustainable synaptic connections mediated by the prion-like transformation of the translational regulator protein CPEB3 (cytoplasmic polyadenylation element binding protein isoform 3) in mammals. The N-terminal prion domain of CPEB3, composed of the two prion subdomains PRD1 and PRD2, has previously been demonstrated to play a crucial role in imparting prion-like properties to the protein. We have already reported the amyloid core of the first prion subdomain (PRD1) of mouse CPEB3. Here, we have investigated the aggregation properties and the structural characteristics of the mouse PRD2 (mPRD2) in vitro. We found that mPRD2 undergoes phase separation at very low concentrations. Interestingly, mPRD2 formed stable, amyloid-like solid condensates instead of the typical liquid condensate formation. Solid-state NMR and other biophysical studies revealed the existence of mixed secondary structures for mPRD2 in the condensates. We propose that the distinct phase separation behavior of mPRD2 would be due to the conformational changes attributed to the pattern of the mPRD2 amino acid sequence, resulting in the formation of rigid, amyloid-like self-assembly.

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来源期刊
ACS Chemical Neuroscience
ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL
CiteScore
9.20
自引率
4.00%
发文量
323
审稿时长
1 months
期刊介绍: ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research
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