氨酸117残留物对肝细胞核因子1α的功能至关重要
Yuan Chu1,2, Long Zhao1, Xian Liu1,2
1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China.
Diabetes
|July 13, 2023
概括
肝细胞核因子1α (HNF1α) 中的lysine 117突变对其功能至关重要,导致糖尿病和类似MODY3.3的发育问题. 这项研究揭示了HNF1α.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 内分泌学 在内分泌学.
背景情况:
- 肝细胞核因子1α (HNF1α) 突变与年轻人成熟期糖尿病 (MODY3) 有关.
- 氨酸117 (K117) 在HNF1α功能中的特定作用及其与MODY3的关联尚未得到充分理解.
- 对于HNF1α K117E变种,之前没有功能数据.
研究的目的:
- 调查氨酸117在HNF1α中的功能意义.
- 阐明在疾病发病过程中的 HNF1α K117E 突变背后的分子机制.
- 通过功能性研究,确定HNF1α K117E变种和MODY3之间的联系.
主要方法:
- 生成一种表达HNF1α K117E突变的动物模型.
- 局部定向突变生成,以产生特定的K117E变种.
- 对同卵性和异卵性突变小鼠的表型分析,包括代谢和发育评估.
主要成果:
- HNF1α K117E同卵性小鼠表现出矮体,肝功能障碍,脏Fanconi综合征和衰竭综合征.
- 同性卵性突变者发展出早期发病的糖尿病与相对胰岛素缺乏,反映MODY3.3.
- 异卵性突变体表现出依赖年龄的葡萄糖不耐受性,与MODY3病原体相一致.
- 通过破坏二分化,K117E突变显著损害了HNF1α的交换活化和DNA结合.
结论:
- 氨酸117对HNF1α的整体功能至关重要,包括它在发育和新陈代谢中的作用.
- HNF1α K117E突变破坏了同位体化,导致DNA结合和交换活化能力降低.
- 这些发现为HNF1α相关疾病的分子基础提供了关键的见解,例如MODY3.3.
更多相关视频
相关概念视频
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Liver Physiology
663
The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
663
Conserved Binding Sites
4.2K
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...
4.2K
Cell Specific Gene Expression
13.6K
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...
13.6K
Co-activators and Co-repressors
7.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K
Transducer Mechanism: Nuclear Receptors
1.4K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.4K


