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中文摘要
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这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者(PI)可能从另一个NIH来源获得了主要资金, 因此可在其他CRISP条目中表示。所列机构为 研究中心,而研究中心不一定是研究者所在的机构。 所有生物都表达那些在特定时刻最需要其产品的基因。为了节省资源并提供对环境条件的高度适应性,生物体开发了不同的系统来感知各种物理和化学线索,并将它们传递给提供基因选择性表达的机器。虽然通常的传感功能是由蛋白质,最近发现的调控电路涉及mRNA区域,称为核糖开关,能够直接和特异性结合的细胞代谢物。核糖开关存在于生命的所有王国中,并且在细菌(包括致病物种)中高度丰富,其中它们响应于各种代谢物(包括辅酶、氨基酸、糖和核碱基)指导许多重要基因的表达。每个核糖开关折叠成进化保守的三维结构,通过与同源代谢物的相互作用而稳定。由于核糖开关通过其结构中的构象重排来调节基因表达,因此我们的研究集中在核糖开关-配体复合物的三维结构的确定上。这些结构将揭示核糖开关控制基因表达的分子原理,并可能有助于合理设计新型代谢物样抗生素。
英文摘要
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. All living beings express those genes whose products are needed most at the given moment. To save resources and provide high adaptability to environmental conditions, organisms developed different systems to sense various physical and chemical cues and transmit them to the machinery that provides selective expression of genes. Though typically the sensing function is performed by proteins, recently discovered regulatory circuits involve mRNA regions, termed riboswitches, capable of direct and specific binding of cellular metabolites. Riboswitches are present in all kingdoms of life, and highly abundant in bacteria, including pathogenic species, where they direct expression of many vital genes in response to various metabolites, including coenzymes, amino acids, sugars, and nucleobases. Each riboswitch is folded into an evolutionary conserved three-dimensional structure stabilized by the interaction with the cognate metabolite. Since riboswitches modulate gene expression through conformational rearrangements in their structures, we have focused our research on the determination of the three-dimensional structures of the riboswitch-ligand complexes. The structures will uncover the molecular principles of riboswitch-controlled gene expression and may help in the rational design of novel classes of metabolite-like antibiotics.
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STRUCTURAL STUDIES OF RIBOSWITCHES
RNA RECOGNITION BY LA AUTOANTIGEN
STRUCTURAL ANALYSIS OF CARBON-CARBON BOND FORMATION CATALYZED BY RIBOZYME
RIBOSWITCHES
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