控制在生物分子凝聚物中的界面蛋白质吸附,脱附和聚合
Brent S Visser1, Merlijn H I van Haren1, Wojciech P Lipiński1,2
1Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
Nature communications
|November 19, 2025
概括
在凝结体接口的α-synuclein (αSyn) 蛋白聚合加速了与年龄相关的疾病. 通过改变表面电荷或竞争性结合等策略调节这种吸附,可以减缓有害蛋白质聚合.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 蛋白质聚合,特别是像α-synuclein (αSyn) 这样的amyloidogenic蛋白质,与各种与年龄有关的神经退行性疾病有关.
- 生物分子凝聚物及其接口可以影响蛋白质聚合动力学,往往促进更快的聚合.
- 了解缩物界面上的αSyn局部化机制对于治疗干预至关重要.
研究的目的:
- 为了阐明αSyn吸附到基于的异型凝结体接口的机制.
- 确定控制αSyn局部化的因素,包括凝结物特性和蛋白质特性.
- 设计和测试调节在凝结体接口上的αSyn积累的策略.
主要方法:
- 研究了αSyn对基于的异型凝聚物的吸附.
- 分析了凝结物表面电荷和蛋白质两性对吸附的影响.
- 量化的吸附可逆性和度依赖性.
- 设计和实施了涉及生物分子添加,竞争性蛋白质吸附和膜优先结合的策略.
主要成果:
- αSyn对凝结表面的定位是一种可逆的多层吸附过程.
- 吸附是由凝结物的表面电荷和αSyn的两性质决定的,在微分子度下稳定.
- 策略包括降低凝聚物z-潜力 (例如,与NTPs,RNA),竞争性吸附 (例如,G3BP1,Hsp70) 和膜偏好的结合有效调节αSyn积累.
- 从凝结体接口中去除αSyn显著降低了聚合率.
结论:
- 对凝结体接口的αSyn吸附是与年龄相关疾病加速聚合的关键驱动因素.
- 调节凝结物表面特性和使用竞争性结合剂是控制αSyn积累的可行策略.
- 这些发现为神经退行性疾病提供了潜在的治疗途径,通过准蛋白质凝结物相互作用.
相关概念视频
02:35Noncovalent Attractions in Biomolecules
63.0K
Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
63.0K
01:26Membrane Fluidity
14.4K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
14.4K
02:04Protein-protein Interfaces
14.4K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
14.4K
01:09Colloidal precipitates
4.8K
The high insolubility of some precipitates can result in an unfavorable relative supersaturation. This can lead to colloidal particles with a large surface-to-mass ratio, where adsorption is promoted. For instance, in the precipitation of silver chloride, silver ions are adsorbed on the surface of the colloidal particles, forming a primary layer. This layer attracts ions of opposite charge (such as nitrate ions), forming a diffuse secondary layer of adsorbed ions. This electric double layer...
4.8K