Protein structure formation studied by time-resolved infrared spectroscopy (A02)

通过时间分辨红外光谱研究蛋白质结构形成（A02）

• 批准号: 211179397
• 金额: --
• 依托单位: Arbeitsgruppe Biophysikalische Chemie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/211179397?language=en
• 关键词: Protein; structure; formation; studied; time

Understanding the molecular mechanisms of protein folding, misfolding and aggregation is the major objective of this project. We develop time-resolved infrared-spectroscopic techniques to study structure formation on different time scales. Formation of  sheets are analysed on the level of individual amino acids using model peptides and site-specific probes. We design peptide templates with polyglutamine (polyQ) sequences to mimic monomeric structural motifs of a fibril. Backbone ordering and side chain packing will be studied separately in order to shed light onto fibril formation in polyQ diseases. Furthermore, we will extend our IR studies on the intrinsically disordered Parkinson disease protein -synuclein and explore the potential regulatory role of other naturally occurring synuclein variants within the aggregation process. Interaction of aggregates with membranes and membrane damage will be characterized in molecular details.

了解蛋白质折叠，错误折叠和聚集的分子机制是这个项目的主要目标。我们开发了时间分辨红外光谱技术来研究不同时间尺度上的结构形成。使用模型肽和位点特异性探针在单个氨基酸的水平上分析折叠的形成。我们设计了具有聚谷氨酰胺（polyQ）序列的肽模板来模拟原纤维的单体结构基序。主链排序和侧链包装将分别研究，以阐明原纤维形成polyQ疾病。此外，我们将扩展我们的IR研究的本质上无序的帕金森病蛋白α-突触核蛋白，并探讨其他自然发生的突触核蛋白的变体在聚集过程中的潜在调节作用。聚集体与膜的相互作用和膜损伤将在分子细节中表征。