变形蛋白的热力学进化:对人类淋巴细胞的理论计算研究
Laura Zanetti-Polzi1, Isabella Daidone2, Claudio Iacobucci2
1Center S3, CNR-Institute of Nanoscience, Via Campi 213/A, 100190, Modena, Italy.
The protein journal
|May 26, 2023
概括
变形蛋白质,如人类的淋巴动素,可以在不同的蛋白质折叠之间切换. 分子动力学模拟揭示了配置和自由能量景观如何驱动这些折叠变化,解释了实验观测.
科学领域:
- 结构生物学是结构生物学.
- 计算生物物理学的计算生物物理.
- 蛋白质动力学 蛋白质动力学
背景情况:
- 变形蛋白质表现出多个生理上相关的折叠.
- 人类化学因子XCL1 (淋巴动素) 是一种具有两个原生状态的变形蛋白质:一个[公式:查看文本]和一个[公式:查看文本]折叠.
- 这两个在生理条件下具有相似的稳定性.
研究的目的:
- 提供人类淋巴细胞的形状热力学结构的详细描述.
- 分析人类淋巴细胞与其祖先之一之间的热力学差异.
- 用计算方法来解释实验观察到的结构平衡的变化.
主要方法:
- 扩展的分子动力学 (MD) 模拟.
- 原子波动的主要组成部分分析 (PCA).
- 基于配置体积和自由能量景观的热力学建模.
主要成果:
- 基于MD的热力学成功地解释了实验观察到的淋巴动素及其祖先之间的结构平衡转移.
- 计算数据提供了对这种蛋白质家族内的热力学演变的解释.
- 该研究强调了配置和自由能量景观在基本空间中的形状的重要性.
结论:
- 分子动力学模拟为了解变形蛋白质的结构热力学提供了强大的工具.
- 这一发现阐明了在淋巴细胞中调节折叠交换的分子机制.
- 这项研究加深了我们对蛋白质可塑性及其进化影响的理解.
相关概念视频
Mechanical Protein Functions
5.0K
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.
5.0K
Bacterial Protein Maturation
43
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
43
Energy to Drive Translocation
2.1K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.1K
Diversity of Archaea IV
60
Hyperthermophilic archaea are a group of extremophiles thriving at temperatures above 80°C, often in hydrothermal vents and volcanic soils where conditions surpass the boiling point of water. At such temperatures, proteins, membranes, and DNA in most organisms degrade, but hyperthermophiles have evolved remarkable adaptations to maintain stability and function.Unique Cellular FeaturesHyperthermophilic membranes are composed of a monolayer of biphytanyl tetraether lipids, which resist...
60
Protein Diffusion in the Membrane
4.4K
Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
4.4K


