相互冲突的界面静电相互作用作为调节远程域间通信的设计原则
Adithi Kannan1, Dhruv Kumar Chaurasiya1, Athi N Naganathan1
1Department of Biotechnology, Bhupat & Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.
ACS bio & med chem Au
|February 26, 2024
概括
改变FF3-FF4蛋白界面上的静电相互作用显著提高了稳定性,加快了折叠. 这一发现为设计具有更好的连接性和合作性的蛋白质提供了洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 蛋白质动力学 蛋白质动力学
背景情况:
- 多域蛋白中的域间通信对于功能和全ostery至关重要.
- 在域界面上的静电相互作用可以调解域间连接.
- 作为一个模型系统,p190A RhoGAP蛋白的FF3-FF4域作为一个模型系统.
研究的目的:
- 研究FF3-FF4接口的静电相互作用如何影响蛋白质的稳定性,折叠和动态.
- 探索保护电荷网络在塑造蛋白质原生组合中的作用.
- 了解工程蛋白质的设计原理,以增强域间通信.
主要方法:
- 位点导向的突变发生 (电荷逆转突变).
- 测量蛋白质稳定性和折叠动力学 (例如,循环二极化,光).
- 计算建模用于分析静电相互作用和形态景观.
主要成果:
- 野生型FF34表现出缓慢的折叠,低的合作性和明显的稳定性,这是由于FF3-FF4接口上的电静电网络 (电荷特洛伊卡) 受到挫败.
- 这个网络在崎的能源环境中促进了多个脱的结构状态.
- 电荷逆转突变破坏了受挫的网络,显著提高了稳定性和合作性,并加速了折叠的数量.
- 突变在全球范围内减轻了波动.
结论:
- 保守的,非最佳的界面静电相互作用塑造了双叶蛋白质的本土组合.
- 调节这些相互作用可以控制蛋白质的稳定性,合作性和折叠动态.
- 这项工作为设计具有可调节的远程连接和合作性的分子系统提供了基础.
相关概念视频
Interfacial Electrochemical Methods: Overview
247
Interfacial electrochemical methods focus on the phenomena occurring at the boundary between an electrode and a solution, as opposed to bulk methods that concentrate on the solution's overall properties. These interfacial methods are classified as either static or dynamic based on the presence of a nonzero current in the electrochemical cell and the consistency of analyte concentrations. Static methods, such as potentiometry, measure the cell's potential without any significant current...
247
Electrostatic Boundary Conditions in Dielectrics
1.2K
When an electric field passes from one homogeneous medium to another, crossing the boundary between the two mediums imparts a discontinuity in the electric field. This results in electrostatic boundary conditions that depend on the type of mediums the field propagates through.
Consider a case where both the mediums across a boundary are two different dielectric materials. Recall that the electric field and electric displacement are proportional and related through the material's...
Consider a case where both the mediums across a boundary are two different dielectric materials. Recall that the electric field and electric displacement are proportional and related through the material's...
1.2K
Intermolecular Forces
58.3K
Atoms and molecules interact through bonds (or forces): intramolecular and intermolecular. The forces are electrostatic as they arise from interactions (attractive or repulsive) between charged species (permanent, partial, or temporary charges) and exist with varying strengths between ions, polar, nonpolar, and neutral molecules. The different types of intermolecular forces are ion–dipole, dipole–dipole, hydrogen bonds, and dispersion; among these, dipole–dipole, hydrogen...
58.3K
Mechanisms of Membrane Domain Formation
3.0K
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.0K
Design Example
329
The innovation of touch-tone telephony revolutionized the telecommunications industry by replacing the traditional rotary dial with a dual-tone multi-frequency (DTMF) signaling system. This system uses a matrix-style keypad with buttons arranged in four rows and three columns, creating 12 distinct signals each assigned to a pair of frequencies. Each button press results in a simultaneous generation of two sinusoidal tones – one from a low-frequency group (697 to 941 Hz) and one from a...
329
Van der Waals Interactions
63.9K
Atoms and molecules interact with each other through intermolecular forces. These electrostatic forces arise from attractive or repulsive interactions between particles with permanent, partial, or temporary charges. The intermolecular forces between neutral atoms and molecules are ion–dipole, dipole–dipole, and dispersion forces, collectively known as van der Waals forces.
63.9K


