CHARACTERIZATION OF INTERMEDIATES IN AMYLOID FIBRIL FORMATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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。这一建议是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。初步调查表明存在可溶性低聚中间物。SAXS将用于表征前体部分折叠的中间体和早期聚集的寡聚中间体，作为实验条件的函数，特别是与聚集率增加相关的条件。待研究的蛋白质（IgG轻链、α -突触核蛋白、tau、瘦素和胰岛素）都与重要疾病有关。

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.