一个分子臂:整合素的分子曲-不曲机制
1Shanghai Institute of Applied Mathematics and Mechanics, Shanghai Key Laboratory of Mechanics in Energy Engineering, Shanghai Frontier Science Center of Mechanoinformatics, School of Mechanics and Engineering Science, Shanghai University, Shanghai, 200072, China. lizhshu@shu.edu.cn.
Biomechanics and modeling in mechanobiology
|February 3, 2024
概括
整合素激活涉及机械力,但它如何回到其不活跃的曲状态是未知的. 模拟显示,整体蛋白β腿像双脚一样,收缩以曲整体蛋白.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 整合素的激活和失活对于细胞的功能和行为至关重要.
- 众所周知,机械力会诱导整体的不曲和激活.
- 活化整合素自发向后曲的机制仍然不太清楚.
研究的目的:
- 阐明整体的曲-不曲动态背后的分子机制.
- 研究整合素如何从扩展,激活状态过渡到曲,非激活状态.
主要方法:
- 采用了全原子分子动力学模拟.
- 模拟集中在整体或其个别子单元上.
主要成果:
- 发现整合素结构的功能类似于人类的手臂.
- 整合素α子单元充当"骨",而β腿则充当"双脚".
- 整体延伸导致β腿伸展,由于β腿收缩而发生自发曲.
结论:
- 这项研究揭示了整体的曲-不曲机制.
- 提供了关于整合素如何在曲,无活化状态下稳定的新见解.
- 提供了解如何实现稳定的扩展整体状态.
相关概念视频
Activation of Integrins
3.4K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.4K
Mechanisms of Membrane-bending
2.7K
The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
2.7K
Integrins
4.0K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.0K
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
Mechanism of Lamellipodia Formation
2.6K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
2.6K
Tension Response at Adherens Junctions
2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K


