STRUCTURAL FEATURES OF KERATIN AND RELATED INTERMEDIATE FILAMENTS

角蛋白中间丝的结构、功能及表达 人皮肤和其他细胞的相关中间丝 类型，正在调查中。虽然这些蛋白质在许多蛋白质中的作用 遗传病现在已经很好地理解了，进一步的结构研究是 制定合理的治疗方法是必要的。我们已经建造了 一系列与角蛋白相对应的合成肽序列 涉及组装中重要重叠区的链 生物物理结构研究和X射线用长丝 结晶学。其中几个合成肽已经注射了 进入活细胞来探索它们的动态行为。其中一些 作为一种非常特殊的试剂来破坏所有类型的 中间细丝，或仅角蛋白细丝。为了 探索末端结构域序列的功能，我们使用了这两个酵母 混合系统。我们已经表达了角蛋白5和14，以探索它们的 体内的结构和功能。在其他研究中，我们已经确定 涉及II型角蛋白的V1亚区的一部分 在与其他蛋白质交联到角化的细胞被膜上时 复层鳞状上皮，一个协调结构的过程 角蛋白细丝细胞骨架与细胞周缘的组织 在终末分化角质形成细胞中。其他交联剂的分析 揭示角蛋白是附着在桥粒蛋白成分上的 桥粒通过一系列相关的中间丝间接形成 相关蛋白质。

The structure, function and expression of keratin intermediate filaments of human skin, and the related intermediate filaments of other cell types, are being investigated. While the roles of these proteins in many genetic diseases are now well understood, further structural studies are necessary to develop rational approaches to therapy. We have constructed a series of synthetic peptides of sequence corresponding to keratin chains which are involved in the important overlap regions in assembled filaments, for biophysical structural studies, and for use for X-ray crystallography. Several of these synthetic peptides have been injected into living cells to explore their dynamic behavior. Some of these function as very specific reagents for the disruption of all types of intermediate filaments, or of only keratin filaments. In order to explore the functions of end domain sequences, we have used the two yeast hybrid system. We have expressed keratins 5 and 14 to explore their structures and functions in vivo. In other studies, we have determined that a portion of the V1 subdomain region of type II keratins is involved in crosslinking with other proteins to the cornified cell envelope of stratified squamous epithelia, a process which coordinates the structural organization of the keratin filament cytoskeleton with the cell periphery in terminally differentiated keratinocytes. Analyses of other crosslinks reveal that the keratins are attached to the desmoplakin component of desmosomes indirectly through a series of related intermediate filament associated proteins.