人类肌球蛋白中的结构功能范式:单残留物替代如何影响低pO2的NO反应性
Mariano Andrea Scorciapino1, Enrico Spiga, Alessandra Vezzoli
1Department of Chemical and Geological Sciences, University of Cagliari, Monserrato (CA), Italy.
Journal of the American Chemical Society
|May 2, 2013
概括
人类肌球蛋白异型,以一种氨基酸不同,在低氧条件下表现出明显的动态和NO反应性. 这种单一的突变会影响蛋白质的灵活性,影响缺氧时的功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 身体生理学 身体生理学
背景情况:
- 人体肌球蛋白 (Mb) 有多种异型,有两种高度表达的变体.
- 这些异构体在残留物54 (氨酸与谷氨酸) 之间存在差异,该残留物位于远离血红素结合部位的位置.
- 这些异构体在高海拔原住民中的过度表达表明在缺氧中具有潜在的替代功能.
研究的目的:
- 为了研究两个人体肌球蛋白异型之间的功能差异.
- 了解单个氨基酸突变 (残留54) 对肌球蛋白动态和功能的作用.
- 探索肌球蛋白的依赖氧气水平的功能,特别是其氧化 (NO) 反应性.
主要方法:
- 使用电子偏磁共振 (EPR) 光谱学对肌球蛋白异型的比较分析.
- 分子动力学 (MD) 模拟以评估蛋白质动力学和结构变化.
- 在不同氧气局部压力 (pO2) 下,对血电子结构和NO反应性的研究.
主要成果:
- EPR光谱检测揭示了铁和近端丁结合相互作用在酸形式的差异.
- MD模拟显示了两种异构体的显著不同的蛋白质动力学,特别是在没有O2.2的情况下.
- 在残留物54的单一突变改变了CD区域的可塑性,影响了远端结合部位的动态和histidine-gate打开的概率.
- 实验结果显示了NO反应性的显著差异,特别是在非常低的pO2下,与MD发现相关.
结论:
- 人体肌球蛋白异型之间的单氨基酸差异显著影响蛋白质动力学和NO反应性,特别是在低氧条件下.
- 肌球蛋白的功能高度依赖于氧气水平,在缺少和存在O2时观察到不同的行为.
- 这些发现有助于了解肌球蛋白在高海拔环境中的适应机制及其在氧和NO代谢中的作用.
更多相关视频
08:51Intra-cardiac Side-Firing Light Catheter for Monitoring Cellular Metabolism using Transmural Absorbance Spectroscopy of Perfused Mammalian Hearts
Published on: May 12, 2019
05:57Synthesizing Amino Acids Modified with Reactive Carbonyls in Silico to Assess Structural Effects Using Molecular Dynamics Simulations
Published on: April 26, 2024
相关概念视频
Gene Families
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
Cooperative Allosteric Transitions
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...
Protein Denaturation
The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...
Oxygen Transport in the Blood
Hemoglobin (Hb) is a crucial molecule in the human body, consisting of four polypeptide chains, each bound to an iron-containing heme group. This unique structure enables hemoglobin to bind to oxygen, with each molecule capable of combining with four molecules of oxygen, leading to rapid and reversible oxygen loading. When fully loaded with oxygen, it is called oxyhemoglobin, while hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin. As hemoglobin binds oxygen,...
Globular and Fibrous Proteins
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
