MFG-E8:与ps结合蛋白相关的多重结合模式模型
Tiffany Suwatthee1, Daniel Kerr1,2,3, Sofiya Maltseva1
1Department of Chemistry, The University of Chicago, Chicago, IL, USA.
The European physical journal. E, Soft matter
|November 24, 2023
概括
这项研究揭示了乳脂球体EGF因子8 (MFG-E8) 呈现出三种不同的结合方式与脂质膜,受酸 (PS) 可用性和膜包装的影响. 这促进了对膜蛋白相互作用的理解.
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:
- 膜结合蛋白通常表现出两种状态的结合模式 (结合/不结合).
- 一个单一的绑定接口可以显示多个绑定模式,但这些很难区分.
- 乳脂球体EGF因子8 (MFG-E8) 结合脂素 (PS),这是细胞亡和恶性瘤的标志物.
研究的目的:
- 研究MFG-E8与脂质膜的结合方式.
- 阐明影响MFG-E8结合亲和力和合作性的因素.
- 开发一种用于分析多模态蛋白质-脂质相互作用的新模型.
主要方法:
- 采用了脂质囊泡的模型系统,具有不同的酸胺 (PS) 分子分数.
- 采用托芬光光谱转移试验来测量结合亲和力.
- 应用X射线反射性实验来评估膜包装效应.
主要成果:
- 确定了MFG-E8的三个不同的结合模式,每个与特定数量的PS脂质相关.
- 证明了负电荷脂质的可用性增强了MFG-E8的约束性合作性.
- 发现膜包装会影响MFG-E8的结合模式.
结论:
- MFG-E8表现出复杂的,多模式的与脂质膜的结合,而不是简单的两态相互作用.
- 与PS脂质和膜包装的静电相互作用是MFG-E8结合的关键决定因素.
- 开发的方法可以应用于研究其他膜结合蛋白及其与膜属性的相互作用.
相关概念视频
Ligand Binding and Linkage
4.8K
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...
4.8K
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
Assembly of Signaling Complexes
5.8K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.8K
Ligand Binding Sites
12.9K
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...
12.9K
Cooperative Binding of Transcription Regulators
6.4K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.4K
Covalently Linked Protein Regulators
6.8K
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....
6.8K


