INTERMEDIATE FILAMENTS--STRUCTURE, ASSEMBLY AND FUNCTION

描述：在过去的15年里积累了大量的信息 关于细胞的分子结构、组装和细胞生物学 中间纤维(IF)。在过去几年里，细胞生物学， 蛋白质化学和分子遗传学揭示了一个令人印象深刻的 关于IF的结构和组装的信息正文。这个 如果在20世纪80年代阐明的蛋白质结构域，S现在似乎具有重要的 在形成和稳定细丝结构方面的作用。我们现在需要 了解这些角色是什么，以及它们在细胞中是如何受到调节的。Dr。 IP建议继续研究IF的形成机制 蛋白质四聚体、高阶齐聚物、细丝和细丝 并研究这些丰富的细胞骨架元素是如何 与其他蜂窝组件进行功能交互。四个具体目标 提出：(1)分析波形蛋白的尾部结构域及其 在IF组装中的意义；(2)确定亚基组成 神经丝(NF)构建块的体外研究，使用 细菌表达的重组核因子蛋白；(3)确定特异性 在酵母中使用双杂交系统，在波形蛋白IF中相互作用的结构域； 以及(4)了解信息系统和信息系统之间的功能相互作用 桥粒，它们共同赋予组织结构和稳定性。 鉴于这一点，这一信息具有潜在的临床意义。 已知IF基因突变是几种皮肤的基础 疾病。

DESCRIPTION: Much information has accumulated over the last 15 years regarding the molecular structure, assembly and cell biology of intermediate filaments (IFs). Over the past few years, cell biology, protein chemistry and molecular genetics have revealed an impressive body of information regarding the structure and assembly of IFs. The IF protein domains elucidated in the 1980's now appear to have important roles in forming and stabilizing filament structure. We now need to know what those roles are and how they are regulated in the cell. Dr. Ip proposes to continue his studies on the mechanisms of formation of IF protein tetrameres, higher order oligomers, filaments and filament networks, and to investigate how these abundant cytoskeletal elements interact functionally with other cellular components. Four specific aims are proposed: (1) to analyze the tail domain of vimentin and its significance in IF assembly; (2) to determine the subunit composition of the neurofilament (NF) building block by in vitro studies, using bacterially expressed recombinant NF proteins; (3) to define specific interacting domains in vimentin IFs, using a two-hybrid system in yeast; and (4) to understand functional interactions between IFs and desmosomes, which together confer structure and stability to tissues. This information is of potential clinical relevance, given that point mutations in IF genes are known to be the basis of several skin diseases.