相关实验视频

Updated: Jan 7, 2026

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

Published on: May 13, 2020

特定地点的氨酸氧化改变了TDP-43 C端域的结构和相位分离

Busra Ozguney¹, Ryan Z Puterbaugh^2,3, Renjith Viswanathan^2,3

¹Artie McFerrin Department of Chemical Engineering, Texas A&M College of Engineering, College Station, Texas.

bioRxiv : the preprint server for biology

|December 25, 2025

概括

在TARDNA结合蛋白43 (TDP-43) 中的甲氨酸氧化破坏了它的细胞相分离. 不同区域的氧化会影响结构和相互作用,影响神经退行性疾病中的TDP-43功能.

科学领域:

生物化学生物化学
分子生物学分子生物学
神经科学是一个神经科学.

背景情况:

TAR DNA 结合蛋白 43 (TDP-43) 涉及于肌缩侧面硬化症 (ALS) 病理.
通过液态液态相分离 (LLPS),TDP-43形成了功能性的细胞组件.
在TDP-43的C端域 (CTD) 中的氨酸残留物容易受到氧化修饰,可能会影响LLPS.

研究的目的:

研究TDP-43的CTD不同区域中甲酸氧化对其结构和相分离产生影响的精确机制.
为了区分在保存区域 (CR) 和内在无序区域 (IDR) 中的甲酸氧化效应.

主要方法:

核磁共振 (NMR) 光谱分析结构变化.
全原子分子动力学 (MD) 模拟以建模分子间相互作用和相位行为.

主要成果:

在TDP-43的CTD中,所有十个氨酸残留物都容易氧化.
在CR中甲氨酸的氧化破坏了螺旋结构和分子间螺旋关联.
在IDR中甲氨酸的氧化破坏了蛋白质内的远程接触.

结论:

甲氨酸氧化对TDP-43的结构和相位分离有不同的影响,具体取决于区域.
在CR和IDR中甲氨酸的氧化通过不同的机制损害了TDP-43相分离.
甲氨酸作为TDP-43阶段行为的关键氧化还原敏感调节剂,为神经退行性疾病中的氧化应激提供了洞察力.

更多相关视频

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

A Mass Spectrometry-Based Proteomics Approach for Global and High-Confidence Protein R-Methylation Analysis

A Mass Spectrometry-Based Proteomics Approach for Global and High-Confidence Protein R-Methylation Analysis

Published on: April 28, 2022

相关概念视频

Translocation of Proteins into the Mitochondria

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...

Protein Modifications in the RER

Protein Modifications in the RER

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...