在InsP3和氨酸受体中关键域的结构和功能保存
Min-Duk Seo1, Saroj Velamakanni, Noboru Ishiyama
1Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Ontario M5G 1L7, Canada.
Nature
|January 31, 2012
概括
伊诺西-1,4,5-三酸盐受体 (InsP3Rs) 和氨酸受体 (RyRs) 是细胞内通道. 这项研究揭示了InsP3Rs和RyRs之间保留的激活机制,涉及对通道关至关重要的域接口.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 伊诺西-1,4,5-三酸盐受体 (InsP3Rs) 和氨酸受体 (RyRs) 是关键的四重体细胞内Ca2+通道.
- 它们的孔域由大型细胞质结构调节,InsP3R门由InsP3结合启动,需要一个抑制器域 (SD).
- 了解它们激活的结构基础是解读细胞信号的关键.
研究的目的:
- 阐明InsP3Rs和RyRs激活的基础结构机制.
- 为了比较这两个重要的通道家族之间的保存激活通路.
- 确定关键接口和涉及InsP3Rs和RyRs的全门的域.
主要方法:
- 确定了大鼠InsP3R1的氨基终端区域 (NT) 的高分辨率结构 (3.0-3.6 Å),无论是有InsP3结合还是没有InsP3结合.
- 利用突变性研究来证实已识别的接口的功能重要性.
- 在InsP3R和RyR之间使用域交换实验来测试保存功能.
主要成果:
- 在InsP3R1 NT中确定了InsP3-结合核心 (IBC) 和抑制器域 (SD) 之间的两个离散接口 (α和β).
- 这些接口和域安排与RyR1中发现的非常相似,表明结构组织得到保护.
- 突变和域交换证实了α-接口在激活中的关键作用,并揭示了InsP3R和RyR之间的功能保存.
结论:
- 保护了InsP3Rs和RyRs的激活机制,涉及N端区域内域界面的全调制.
- 带结合 (InsP3) 或与疾病相关的突变会诱导形状变化,重定向关键域,最终封闭Ca2+孔.
- 这项研究提供了一个统一的结构框架,以了解这些必不可少的细胞内通道的关门.
相关概念视频
Conserved Binding Sites
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 analyses the...
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 analyses the...
Conserved Binding Sites
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 analyses the...
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 analyses the...
Conservation of Protein Domains Over Different Proteins
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 form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Structural Protein Function
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
Structural Protein Function
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
Conservation of Protein Domains
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 form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...

