评估构造干扰物对β-桶折的折叠和聚合路径的影响
Martín Ballatore1, Adriana Carlucci2, José María Delfino1
1Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires and Institute of Chemistry and Biological Physical Chemistry (IQUIFIB, UBA-CONICET), Junin 956, 1113, Buenos Aires, Argentina.
Biochemical and biophysical research communications
|December 25, 2024
概括
这项研究调查了蛋白质聚合,揭示了化学和物理因素如何影响大鼠肠脂肪酸结合蛋白 (IFABP) 的折叠和聚合途径. 不同的条件可以促进无形或粉样聚合.
科学领域:
- 蛋白质的生物化学 蛋白质的生物化学
- 生物物理化学 生物物理化学
- 分子生物学分子生物学
背景情况:
- 蛋白质的原生折叠和聚合通路对于细胞功能和疾病至关重要.
- 鼠肠脂肪酸结合蛋白 (IFABP) 是一种已知在特定条件下聚合的小β-桶蛋白.
研究的目的:
- 研究物理和化学扰动剂在IFABP折叠和聚合中的相互作用.
- 了解三乙醇 (TFE) 的子聚合度如何影响展开的过渡.
- 为了阐明驱动无形与粉样聚合的机制.
主要方法:
- 差分扫描热量计 (DSC) 用于热变质.
- 使用尿素和化甘 (GdmCl) 的化学变质研究.
- 在不同度的TFE,GdmCl和温度下对蛋白质聚合的分析.
主要成果:
- 在没有聚合的情况下,IFABP的尿素诱导的展开遵循两个状态的过渡.
- 三乙醇 (TFE) 在度超过15%时会诱导粉样类聚合.
- 无论是TFE还是GdmCl都会降低IFABP的稳定性;TFE在加热时促进无形聚合,而单独的GdmCl则没有.
- 同时存在的TFE和GdmCl有利于粉样聚合,可能是由于TFE-GdmCl相互作用和TFE溶解.
结论:
- 无形和粉样聚合途径之间的选择取决于扰剂对蛋白质和溶剂结构的联合作用.
- 热量增强的TFE促进的多溶解在聚合中起作用.
- GdmCl可能通过溶解非原生状态并促进TFE分离来影响聚合,有利于粉样蛋白的形成.
相关概念视频
Protein Folding
7.8K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
7.8K
Molecular Chaperones and Protein Folding
17.7K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
17.7K
Amyloid Fibrils
9.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.2K
Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
Multi-pass Transmembrane Proteins and β-barrels
5.2K
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
5.2K
Protein Organization
136.5K
Overview
136.5K


