EFFECTS OF GLUTAMINES ON THE SELF-ASSEMBLY OF A BETA-HAIRPIN FIBRILS

谷氨酰胺对 β-发夹原纤维自组装的影响

• 批准号: 7598456
• 负责人: Robert Fairman
• 金额: $ 0.08万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598456
• 关键词: Alzheimer' s Disease; Amyloid; Amyloid Fibrils; Atomic Force Microscopy; Biological Models; Circular Dichroism; Computer Retrieval of Information on Scientific Projects Database; Creutzfeldt-Jakob Syndrome; Dementia; Disulfides; Exhibits; Funding; Glutamine; Grant; Hydrogen Bonding; Institution; Modeling; Morphology; Numbers; Proteins; Research; Research Personnel; Resources; Side; Source; Structure; United States National Institutes of Health; amyloid formation; beta pleated sheet; design; human disease; protein misfolding; self assembly; synthetic peptide

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Amyloid fibrils, well-structured aggregates of misfolded protein, have been implicated in a number of prevalent human diseases such as Alzheimer's dementia and Creutzfeldt-Jacob's disease. While formed by a diverse repertoire of proteins and synthetic peptides, including many with glutamine-rich sequences, amyloid fibrils have a common cross-beta-structure. Even with this common arrangement and multiple models for the atomic structure of glutamine-rich amyloid, a dominant set of forces governing amyloid formation and stabilization have not been experimentally determined. Since the forces previously investigated have not included side-chain hydrogen bonding, we created a glutamine-rich model system by de novo design that is capable of these interactions. This model, in a disulfide-cyclized form, forms beta-sheet structures, as shown by circular dichroism, and exhibits a fibril morphology, as shown by atomic force microscopy.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 淀粉样蛋白原纤维是错误折叠蛋白质的结构良好的聚集体，与许多流行的人类疾病如阿尔茨海默氏痴呆症和克-雅二氏病有关。 虽然由多种蛋白质和合成肽形成，包括许多富含谷氨酰胺的序列，但淀粉样蛋白原纤维具有共同的交叉β结构。 即使有了这种常见的安排和富含谷氨酰胺的淀粉样蛋白的原子结构的多个模型，一组主导的力量控制淀粉样蛋白的形成和稳定尚未实验确定。 由于先前研究的力不包括侧链氢键，我们通过从头设计创建了能够进行这些相互作用的富含谷氨酰胺的模型系统。 该模型以二硫化物环化形式形成β-折叠结构，如圆二色性所示，并表现出原纤维形态，如原子力显微镜所示。