CHARACTERIZATION OF INTERMEDIATES IN AMYLOID FIBRIL FORMATION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。我们研究的总体目标是确定蛋白质聚集的分子基础，特别是在蛋白质沉积疾病的背景下。该建议是为了表征淀粉样纤维和无定形聚集体形成过程中的早期中间体。初步研究表明存在可溶性低聚中间物质。SAXS将用于表征前体部分折叠的中间体和早期低聚中间体的聚集，作为实验条件的函数，特别是与聚集速率增加相关的那些。待研究的蛋白质（IgG轻链、α-突触核蛋白、tau、瘦素和胰岛素）都与重要疾病相关。

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. The overall goal of our research is to determine the molecular basis for protein aggregation, especially in the context of protein deposition diseases. This proposal is to characterize early intermediates in the process of amyloid fibril and amorphous aggregate formation. Preliminary investigations suggest the presence of soluble oligomeric intermediate species. SAXS will be used to characterize both the precursor partially-folded intermediates and early oligomeric intermediates in aggregation, as a function of experimental conditions, especially those correlating with increased rates of aggregation. The proteins to be studied (IgG light chains, alpha-synuclein, tau, leptin and insulin) are all associated with important diseases.