Modeling Oligomeric Structures of Amyloid forming Peptides

淀粉样蛋白形成肽的寡聚结构建模

• 批准号: 10702860
• 负责人: Stewart Durell
• 金额: $ 10.6万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702860
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Atomic Force Microscopy; Data; Dimensions; Electrons; Gamma synuclein; Goals; Image; Ion Channel; Lipoproteins; Modeling; Neurons; Paper; Parkinson Disease; Peptides; Publishing; Side; Synuclein Family; Tubular formation; alpha synuclein; amyloid structure; beta barrel; drug development; monomer; phosphoneuroprotein 14

In this period we published two papers. In the first we proposed a range of concentric beta-barrel models and compare their dimensions to image-averaged electron micrographs of Beta-Amyloid42. The smaller oligomers have 6, 8, 12, 16, and 18 monomers. These beads string together to form necklace-like beaded-annular-protofibrils (bAPFs). These gradually morph into smooth-APFs in which a S3 beta-barrel is shielded on one or both sides by beta-barrels formed from S1 and S2 segments. In the second we extend our beta-amyloid peptide models of oligomers, annular protofibrils, tubular protofibrils, lipoproteins, and ion channels to the alpha, beta and gamma synuclein family which has been implicated in Parkinson's Disease.

这期间我们发表了两篇论文。首先，我们提出了一系列同心 β 桶模型，并将它们的尺寸与 β-淀粉样蛋白 42 的图像平均电子显微照片进行比较。较小的低聚物有 6、8、12、16 和 18 个单体。这些珠子串在一起形成项链状的珠状环形原纤维（bAPF）。这些逐渐演变成平滑 APF，其中 S3 β 桶的一侧或两侧被由 S1 和 S2 片段形成的 β 桶屏蔽。在第二部分中，我们将寡聚物、环状原纤维、管状原纤维、脂蛋白和离子通道的β-淀粉样肽模型扩展到与帕金森病有关的α、β和γ突触核蛋白家族。