雷丁醇调节了细胞内雷丁醇结合蛋白的特定位点的移动性,以促进连接体的结合
Tanja Mittag1, Lorella Franzoni, Davide Cavazzini
1J.W. Goethe University, Frankfurt, Germany.
Journal of the American Chemical Society
|July 27, 2006
概括
细胞视网结合蛋白I型 (CRBP) 使用蛋白质动态来快速结合视网. 干结合调节蛋白质的移动性,通过动态访问机制实现高亲和度的视网醇吸收.
科学领域:
- 蛋白质动力学和配体结合相互作用.
- 生物物理学和结构生物学.
- 蛋白质功能的分子机制.
背景情况:
- 蛋白质动态对于蛋白质功能至关重要,特别是在连接体相互作用中.
- 细胞视网结合蛋白I型 (CRBP) 具有很高的亲和力结合视网.
- 显然,CRBP的封闭形状限制了连接体的访问.
研究的目的:
- 为了研究CRBP吸收视网醇的机制.
- 了解蛋白质动力学是如何促进高亲和度联体结合的.
- 阐明特定位点移动性在CRBP-雷丁醇相互作用中的作用.
主要方法:
- 核磁共振 (NMR) 光谱学.核磁共振 (NMR) 光谱学.
- 对NMR信号的线形分析.
- 对apo和holo-CRBP结构进行比较分析.
主要成果:
- 尽管具有封闭的形状,但CRBP能快速与视网结合,并具有很高的亲和力.
- 核磁共振线形状分析揭示了动态形状变化.
- 干结合诱导CRBP的门户区域中的长寿适配体.
结论:
- 蛋白质动力学对于克服带结合中的构造障碍至关重要.
- 通过连接体调节特定位点的移动性,便于高亲和度结合.
- 一个动态的机制,涉及向量形成,允许网醇进入CRBP腔.
相关概念视频
Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
Ligand Binding Sites
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding and Linkage
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Anchoring Junctions
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...


