分子伴侣Hsp90 Hsp90的结构动态的演变
Stefan Riedl1, Ecenaz Bilgen2, Ganesh Agam2
1Center for Protein Assemblies, Department Bioscience, School of Natural Sciences, Technical University Munich, Garching, Germany.
Nature communications
|October 4, 2024
概括
热冲击蛋白90 (Hsp90) 的分子伴侣功能在物种中保持不变,但与酵母Hsp90.0相比,人类Hsp90表现出改变的ATPase循环动力学和结构灵活性.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 进化生物学是进化的生物学.
背景情况:
- 热冲击蛋白90 (Hsp90) 是真核细胞中蛋白质稳态的关键分子伴侣.
- Hsp90的功能和结构从酵母保存到人类,随着进化过程中的共同伴侣和客户端蛋白相互作用的复杂性增加.
研究的目的:
- 为了研究Hsp90的ATPase循环和酵母和人类之间的结构动态的进化变化.
- 确定对人类改变的Hsp90动态负责的特定分子决定因素.
主要方法:
- 在酵母和人类系统中对Hsp90 ATPase循环和形状转换进行比较分析.
- 位点定向的突变发生,以探测特定残留物在Hsp90形状变化和ATPase活性中的作用.
主要成果:
- 虽然Hsp90的ATPase循环的整体形态转换是保留的,但酵母和人类Hsp90.0之间的循环时间和动态显著不同.
- 人类的Hsp90表现出更广泛的形状组合,独立于ATP的存在,与酵母Hsp90.0.不同.
- 在保存的结构元素中发现了两种特定的残留物,它们是改变ATPase速率和人类Hsp90.0的形状转换的关键驱动因素.
- 人类和酵母Hsp90之间的这些残留物的突变交换成功地交换了它们各自的ATPase速率和结构动态.
结论:
- Hsp90已经发展出增强的结构动态,有利于N-终端开放,客户端接受状态.
- 特定的氨基酸替代推动了Hsp90的动态特性和ATPase循环特征的演变.
- 了解这些进化修饰,可以了解Hsp90在更高的真核生物中的适应性和功能.
相关概念视频
03:00Molecular Chaperones and Protein Folding
17.8K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
17.8K
01:25Protein Folding
7.8K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
7.8K
01:37Energy to Drive Translocation
2.0K
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...
2.0K
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
02:41Protein Complex Assembly
10.6K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.6K
02:26Conservation of Protein Domains Over Different Proteins
10.8K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.8K