NOVEL CYSTEINES OF P22 TAILSPIKE PROTEIN

描述：确定蛋白质折叠中间体的性质是 这对于理解蛋白质如何折叠以及为什么会错误折叠至关重要， 确定蛋白质聚集的决定因素。错误折叠或路径偏离 已经鉴定出折叠事件，特别是导致聚集的那些 作为包括囊性纤维化在内的几种人类疾病的病原体， 阿尔茨海默氏病和朊病毒海绵状脑病，如 克-雅二氏病更好地理解 促进折叠和防止聚集将增强罗宾逊博士的能力， 为聚集驱动的疾病设计抑制剂和疗法。 尽管在鉴定小分子中间体的特征方面取得了越来越多的进展， 行为良好的蛋白质，理解折叠和组装大型多结构域 蛋白质仍然是一个关键问题，特别是在后基因组领域。 将在学习中获得的知识和技术转化为 小的蛋白质系统到大的、复杂的蛋白质和寡聚体。 结构和功能基因组学倡议将需要一个更好的 理解低聚物和其他复合物的折叠和组装 蛋白质系统这些蛋白质可能需要新的机制， 辅助折叠，以及评价其中间体的新技术。博士 罗宾逊正在研究P22尾刺蛋白的组装中间体， 一类新的半胱氨酸残基之间的相互作用，指导折叠， 通过瞬时亚基间二硫键形成组装。 P22尾刺蛋白是一个由666个氨基酸组成的同源三聚体。 尾钉在折叠的中间体中形成瞬时二硫键， 在体内和体外的组装途径。二硫键的形成似乎 有利于折叠和不利于聚集，并可能有助于β-片层 在低聚过程中对齐。为了理解瞬态的作用 二硫键的形成尾钉折叠和组装，罗宾逊博士的 一项研究计划将确定二硫键的氨基酸决定簇 在体内和体外形成。罗宾逊博士还将开发一种新的方法 它结合了氰化、蛋白水解裂解和MALDI质谱 以绘制尾钉组装中间体中的二硫键连接性。

DESCRIPTION: Determining the properties of protein folding intermediates is critical to understanding how proteins fold and why they misfold, and to identifying the determinants of protein aggregation. Misfolding or off-pathway folding events, particularly those leading to aggregation, have been identified as the causative agents in several human diseases including cystic fibrosis, Alzheimer's disease, and prion spongiform encephalopathies such as Creutzfeldt-Jacob disease. A better understanding of the interactions which promote folding and prevent aggregation will enhance Dr. Robinson's ability to design inhibitors and therapeutics for aggregation-driven diseases. Despite increasing progress in identifying features of intermediates of small well-behaved proteins, understanding folding and assembly of large multi-domain proteins is still a critical problem, particularly in the post-genomic area. There is limited ability to translate the knowledge and techniques gained in small protein systems to those of large, complex proteins and oligomers. Structural and functional genomics initiatives will require a better understanding of the folding and assembly of oligomers and other complex protein systems. It is likely that such proteins require novel mechanisms which assist folding, and novel techniques to evaluate their intermediates. Dr. Robinson is investigating assembly intermediates of P22 tailspike protein, and a novel class of interactions between cysteine residues that direct folding and assembly through transient intersubunit disulfide bond formation. P22 tailspike protein is an homotrimer of 666 amino acids per monomer chain. Tailspike forms transient disulfide bonds in an intermediate on the folding and assembly pathway in vivo and in vitro. Disulfide bond formations appear to facilitate folding and disfavor aggregation, and may help in beta-sheet alignment during oligomerization. In order to understand the role of transient disulfide bond formation in tailspike folding and assembly, Dr. Robinson's research program will identify amino acid determinants of disulfide bond formation in vivo and in vitro. Dr. Robinson will also develop a novel method which combines cyanylation, proteolytic cleavage, and MALDI mass spectroscopy to map disulfide bond connectivity in tailspike assembly intermediates.