来自β-氨基的的寡合体结构
Johnny D Pham1, Nicholas Chim, Celia W Goulding
1Department of Chemistry, University of California, Irvine, Irvine, California 92697-2025, USA.
Journal of the American Chemical Society
|August 10, 2013
概括
研究人员使用宏环稳定了amyloid-β (Aβ) 寡合体,通过X射线晶体学揭示了它们的结构. 这些发现提供了关于粉样蛋白疾病和潜在的膜相互作用的见解.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 神经科学是一个神经科学.
背景情况:
- 粉样蛋白寡合体与阿尔茨海默病和其他粉样蛋白病理有关.
- 这些异质和不稳定的粉样物种的精确结构仍然不太清楚.
研究的目的:
- 为了阐明粉样β (Aβ) 寡合体的结构特征.
- 研究Aβ寡合体的组合及其在疾病发病过程中的潜在作用.
主要方法:
- 将一个关键的氨基基原蛋白Aβ区域纳入稳定性宏环中.
- 使用X射线晶体学对宏循环结合的寡合物的结构性确定.
- 分子建模用于预测天然Aβ寡合物的结构.
主要成果:
- 确定了宏环Aβ ((15-23)) 类寡合体及其组合的晶体结构.
- 寡合体形成了与结合的β片,组装成十字形四合体,随后是三角形十二合体.
- 进一步的晶格组装导致六角孔,分子建模表明自然Aβ的类似结构.
结论:
- 该研究揭示了Aβ寡合体及其组合的详细结构,为了解它们在粉样蛋白疾病中的作用提供了基础.
- 鉴定的寡合体结构表明与细胞膜的潜在相互作用.
- 获得的见解可以为针对粉样蛋白疾病的治疗策略提供信息.
相关概念视频
Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Protein Organization
Overview
Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
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...
Peptide Bonds
A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...


