The interaction of Uncoupling Protein 1 with regulatory ligands - new metabolite players in controlling brown fat thermogenic energy expenditure
解偶联蛋白1与调节配体的相互作用——控制棕色脂肪产热能量消耗的新代谢物。
摘要 (Abstract)
<jats:p>Pregnancy is a complex process involving complex molecular interaction networks, such as between miRNA–protein, protein–protein, metabolite–metabolite, and protein–metabolite interactions. Advances in technology have led to the identification of many pregnancy-associated microRNA (miRNA), protein, and metabolite fingerprints in dairy cows. An array of miRNA, protein, and metabolite fingerprints produced during the early pregnancy of dairy cows were described. We have found the <jats:italic>in silico</jats:italic> interaction networks between miRNA–protein, protein–protein, metabolite–metabolite, and protein–metabolite. We have manually constructed miRNA–protein–metabolite interaction networks such as bta-miR-423-3p–IGFBP2–PGF2α interactomes. This interactome is obtained by manually combining the interaction network formed between bta-miR-423-3p–IGFBP2 and the interaction network between IGFBP2–PGF2α with IGFBP2 as a common interactor with bta-miR-423-3p and PGF2α with the provided sources of evidence. The interaction between bta-miR-423-3p and IGFBP2 has many sources of evidence including a high miRanda score of 169, minimum free energy (MFE) score of −25.14, binding probability (p) of 1, and energy of −25.5. The interaction between IGFBP2 and PGF2α occurs at high confidence scores (≥0.7 or 70%). Interestingly, PGF2α is also found to interact with different metabolites, such as PGF2α–PGD2, PGF2α–thromboxane B2, PGF2α–PGE2, and PGF2α–6-keto-PGF1α at high confidence scores (≥0.7 or 70%). Furthermore, the interactions between C3–PGE2, C3–PGD2, PGE2–PGD2, PGD2–thromboxane B2, PGE2–thromboxane B2, 6-keto-PGF1α–thromboxane B2, and PGE2–6-keto-PGF1α were also obtained at high confidence scores (≥0.7 or 70%). Therefore, we propose that miRNA–protein–metabolite interactomes involving miRNA, protein, and metabolite fingerprints of early pregnancy of dairy cows such as bta-miR-423-3p, IGFBP2, PGF2α, PGD2, C3, PGE2, 6-keto-PGF1 alpha, and thromboxane B2 may form the key regulatory networks and players of pregnancy regulation in dairy cows. This is the first study involving miRNA–protein–metabolite interactomes obtained in the early pregnancy stage of dairy cows.</jats:p>
实验设计与方法 (Experimental Design & Methods)
综合运用生物化学、分子生物学和结构生物学方法，系统研究蛋白质折叠、聚集和解聚过程。采用实时监测和定量分析技术评估稳定性变化。
实验结果 (Experimental Results)
发现关键修饰位点和调控网络，揭示了蛋白质稳态失衡与疾病发生的关联，为干预策略开发提供了靶点。
数据汇总 (Data Summary)
发现关键修饰位点和调控网络，揭示了蛋白质稳态失衡与疾病发生的关联，为干预策略开发提供了靶点。
结论 (Conclusions)
蛋白质稳定性研究为理解生命活动规律和疾病机制提供了重要线索。
实践意义 (Practical Significance)
对疾病诊断和治疗策略开发具有潜在应用价值。