STRUCTURE OF PROTEINS THAT REGULATE TRANSCRIPTION

转录的启动是基因转录的主要环节之一 基因表达的调控。特定蛋白质-DNA和蛋白质-蛋白质 相互作用决定了哪些基因在正常和 不正常的情况。这些大分子之间的相互作用是 由它们的三维结构决定。因此，一个 蛋白质-DNA和蛋白质-蛋白质相互作用的分子理解 它们是基因调控等基本过程的核心 要想表达，需要了解 所涉及的大分子。 拟议的研究将利用X射线结晶学技术来 确定了化合物的三维结构 含多种寡核苷酸的噬菌体Lambda Cro抑制子。 这些结构研究将产生关于蛋白质的详细信息- 当像Cro这样的蛋白质在碱基上结合DNA时可能发生的DNA相互作用 序列独立的方式或特定的碱基序列。因为它 将在许多年后才能确定所有参与其中的蛋白质的结构 基因表达的调控是已知的，必须选择模型系统 这将提供一般信息。CRO抑制器提供了一个 研究蛋白质-DNA分子基础的优秀体系 互动。 这项研究的第二个长期目标是检查 识别特定碱基序列的转录调控蛋白 激活或抑制RNA聚合酶的作用。影响 特定基因的转录，调控蛋白 必须与特定的碱基序列结合才能传递给RNA 聚合酶。一种负责在体内产生信使核糖核酸的酶 真核生物，RNA聚合酶II，含有一种不寻常的重复氨基酸 将使用荧光能量转移测量来检查序列 和计算机建模。然后，可以将该结构信息与 RNA聚合酶II的这一部分在启动中的功能作用 转录和基因表达的调控。

The initiation of transcription is one of the primary points for the regulation of gene expression. Specific protein-DNA and protein-protein interactions determine which genes are expressed in both normal and abnormal conditions. These interactions between macromolecules are determined by their three dimensional structures. Consequently, a molecular understanding of the protein-DNA and protein-protein interactions that are the core of a fundamental process like the regulation of gene expression requires a knowledge of the three-dimensional structures of the macromolecules that are involved. The proposed research will utilize X-ray crystallographic techniques to determine the three-dimensional structures of complexes of the bacteriophage lambda Cro repressor with a variety of oligonucleotides. These structural studies will generate detailed information on the protein- DNA interactions that can occur when proteins like Cro bind DNA in a base sequence independent fashion or to specific base sequences. Because it will be many years before the structures of all the proteins involved in the regulation of gene expression are known, model systems must be chosen that will provide general information. The Cro repressor provides an excellent system for studying the molecular basis for protein-DNA interactions. A second long term objective of the research is to examine how transcriptional regulatory proteins that recognize specific base sequences of DNA activate or repress the action of RNA polymerase. To affect transcription of a specific gene, the information that regulatory proteins are bound to particular base sequences must be transmitted to RNA polymerase. The enzyme responsible for the production of mRNA in eucaryotes, RNA polymerase II, contains an unusual repeating amino acid sequence will be examined using fluorescence energy transfer measurements and computer modelling. This structural information can then be related to the functional role of this portion of RNA polymerase II in the initiation of transcription and the regulation of gene expression.