艾拉218Val变体对NG蛋白质的破坏性影响
Jared Truitt1, Cynthia L Stenger2, Luke Terwilliger1
1CSIS, University of North Alabama, Florence, Alabama, United States.
microPublication biology
|March 13, 2025
概括
遗传性出血性长膜炎 (HHT) 与 ENG 基因有关. 预计一种特定的变种,Ala218Val,可能具有致病性,影响动脉发育并导致出血障碍.
科学领域:
- 遗传学和分子生物学
- 心血管生物学 心血管生物学
- 生物信息学是一种生物信息学.
背景情况:
- 遗传性出血性长膜炎 (HHT) 是一种影响血管形成的自体主导性疾病.
- ENG基因编码内分泌物,对适当的动脉发育和重塑至关重要.
- 内分泌蛋白的缺陷会导致脑膜切开,导致鼻子和重要器官出血.
研究的目的:
- 为了研究与HHT相关联的ENG基因中不确定的意义的特定变异的致病性.
- 在计算上对Ala218Val误解变体进行表征.
主要方法:
- 使用了in silico病原性预测工具.
- 进行了结构残留的保存分析.
- 使用分子动力学模拟 (MDS) 来评估变异对蛋白质结构和动力学的影响.
主要成果:
- 在 ENG 基因中的 Ala218Val 替代位点在各个物种中高度保存,位于埋藏的结构区域.
- 与模拟水环境中的野生类型相比,MDS揭示了Ala218Val变体的蛋白质动态变化.
结论:
- 预计Ala218Val变种可能具有病原性.
- 计算分析表明,这种变体破坏了正常的内分泌物功能,可能导致HTH的发病.
更多相关视频
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.4K
09:10A Fast and Quantitative Method for Post-translational Modification and Variant Enabled Mapping of Peptides to Genomes
Published on: May 22, 2018
9.1K
相关概念视频
Allosteric Proteins-ATCase
5.6K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.6K
Ligand Binding and Linkage
4.7K
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...
4.7K
Leaky Scanning
5.0K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.0K
Conserved Binding Sites
4.1K
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...
4.1K
Cell Specific Gene Expression
13.4K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.4K
Conservation of Protein Domains Over Different Proteins
10.7K
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...
10.7K
