Methyl TROSY of alanine residues in large protein complexes: development and application

大蛋白质复合物中丙氨酸残基的甲基TROSY：开发和应用

• 批准号: BB/G004668/1
• 负责人: Steve Matthews
• 金额: $ 42.11万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG004668%2F1
• 关键词: Methyl; TROSY; alanine; residues; large

DNA is the building block of the life and contains all the information that the cells require to manufacture proteins. An intermediate language exists in the sequence of RNA that translates a gene's message into a protein's amino acid sequence. The process of producing RNA is called transcription and is the most important regulatory step in gene expression in organisms ranging from simple bacteria to humans. The protein RNA polymerase (RNAP) is the enzyme which catalyses transcription and is the target, directly or indirectly, of most regulation of gene expression. The cells that make up our bodies are highly regulated and dynamic systems. In and around cells, functions are determined by the interplay of different types of biomolecules, such as proteins. These interactions are possible through the recognition of specific, complementary surfaces at the atomic level. For a better understanding of these cellular mechanisms, researchers need to develop new technologies for the study of biomolecules. In particular, modern molecular techniques like nuclear magnetic resonance (NMR) offer a powerful method to determine the different shapes (or conformations) and motion (or dynamics) of molecules and the interactions between them. In this proposal we aim to develop a novel application of NMR that can be applied and analysed on very large biomolecules, such as RNAP. The structural detail provided by these techniques is also sufficient for the elucidation of enzymatic mechanisms (e.g. the series of steps required for the synthesis and degradation of new molecules) and to analyse the interaction of biomolecules. We will exploit this new methodology to understand more about how viruses can interfere with the activity for the RNAP in order to alter gene expression to serve its own needs

DNA 是生命的基石，包含细胞制造蛋白质所需的所有信息。 RNA序列中存在一种中间语言，它将基因的信息翻译成蛋白质的氨基酸序列。产生 RNA 的过程称为转录，是从简单细菌到人类等生物体中基因表达最重要的调控步骤。蛋白质RNA聚合酶(RNAP)是催化转录的酶，并且是大多数基因表达调节的直接或间接靶标。构成我们身体的细胞是高度调控的动态系统。细胞内部和周围的功能是由不同类型的生物分子（例如蛋白质）的相互作用决定的。这些相互作用可以通过在原子水平上识别特定的互补表面来实现。为了更好地了解这些细胞机制，研究人员需要开发用于研究生物分子的新技术。特别是，核磁共振（NMR）等现代分子技术提供了一种强大的方法来确定分子的不同形状（或构象）和运动（或动力学）以及它们之间的相互作用。在本提案中，我们的目标是开发一种新的 NMR 应用，可以应用于和分析非常大的生物分子，例如 RNAP。这些技术提供的结构细节也足以阐明酶促机制（例如新分子的合成和降解所需的一系列步骤）并分析生物分子的相互作用。我们将利用这种新方法来更多地了解病毒如何干扰 RNAP 活性，从而改变基因表达以满足自身需求

项目成果

Automated assignment in selectively methyl-labeled proteins.

• DOI: 10.1021/ja9020233
• 发表时间: 2009-07-15
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Xu Y;Liu M;Simpson PJ;Isaacson R;Cota E;Marchant J;Yang D;Zhang X;Freemont P;Matthews S
• 通讯作者: Matthews S

TROSY NMR spectroscopy of large soluble proteins.

• DOI: 10.1007/128_2011_228
• 发表时间: 2013
• 期刊: Topics in current chemistry
• 影响因子: 8.6
• 作者: Yingqi Xu;S. Matthews