STRUCTURE/FUNCTION OF THE LEUCINE ZIPPER MOTIF

描述：（改编自研究者摘要）本提案 集中在最近描述的结构基序，称为“亮氨酸 拉链”，这是发现在一些DNA结合蛋白。 长期 本研究的目的是了解 亮氨酸拉链的结构和功能之间的关系， 这类新的蛋白质以序列特异性方式结合DNA。 的 这项研究对于理解蛋白质-DNA具有重要意义 相互作用，特异性蛋白质-蛋白质相互作用，转录 激活和肿瘤发生。 本研究的具体目的是：（1） 为了确定对应于所述肽的合成肽的结构， 酵母转录激活因子GCN 4的亮氨酸拉链区， 使用晶体学（与晶体学家合作）和2D-NMR 方法;（2）确定GCN 4的60个残基片段，包括 亮氨酸拉链能够以序列特异性结合DNA， 方式，使用2D-NMR和诱变研究：和（3）以确定 两个亮氨酸拉链肽形成特异性异二聚体的机制 对应于核致癌基因产物Fos和Jun的区域， 使用结构研究和变体肽的合成。

DESCRIPTION: (Adapted from the Investigator's Abstract) This proposal focuses on a recently described structural motif, called the "leucine zipper", that is found in some DNA binding proteins. The long-term objectives of the proposed research are to understand the relationship between structure and function in leucine zippers, and to understand how this new class of proteins bind DNA in a sequence specific manner. The proposed research is significant for understanding protein-DNA interactions, specific protein-protein interactions, transcriptional activation, and oncogenesis. The specific aims of the research are: (1) to determine the structure of a synthetic peptide corresponding to the leucine zipper region of a yeast transcriptional activator called GCN4, using crystallography (in collaboration with a crystallographer) and 2D-NMR methods; (2) to determine how a 60-residue fragment of GCN4, that includes the leucine zipper, is capable of binding DNA in a sequence-specific manner, using 2D-NMR and mutagenesis studies: and (3) to determine the mechanism for specific heterodimer formation by two leucine zipper peptides that correspond to regions of the nuclear oncogene products Fos and Jun, using structural studies and synthesis of variant peptides.