CONFORMATIONAL ANALYSIS OF RIBOSWITCH APTAMERS BY SAXS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本年度GUP-21939：本GUP是GUP 11627（2008）和GUP 12457（2009）的后续研究，其中我们检查了结合同源小分子后核糖开关构象变化的拟议一般特征。 核糖开关是基因调节mRNA结构域，其通过调节细菌中的转录或翻译以及真核生物中的前体mRNA剪接或聚腺苷酸化来响应其同源小分子的细胞内浓度。 对于所有的核糖开关类检查，系统发育序列分析描绘了一段高度保守的序列，这是必要的和足够的特异性在体外结合到其同源代谢物。 这些特异性结合结构域或适体一直是研究核糖开关机制和功能的中心焦点。 构象变化被认为是核糖开关功能的组成部分。 小角X射线散射是一种探测这种构象变化的全局性质的技术。 最近，几个实验室已经发表了论文，利用这种技术来了解几种核糖开关RNA的代谢诱导的结构反应。 目前的提案与GUP 12457和GUP 11627有关，两者的标题都是“Investigating the proposed 'switching' mechanism of various riboswitches”。 先前的GUP（为其分配了射束时间）专注于检查核糖开关功能的拟议一般特征。 SAXS分析揭示了各种核糖开关对其各自的小分子效应物的特异质应答，如我们最近的出版物中所述（Baird和Ferre-D 'Amare，RNA，2010; Kulshina等，NSMB，2009）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Current year GUP-21939: This GUP is a follow-up to GUP11627(2008) and GUP12457 (2009) in which we examined the proposed general features of riboswitch conformational change upon binding cognate small-molecules. Riboswitches are gene-regulatory mRNA domains that respond to the intracellular concentration of their cognate small molecules by modulating transcription or translation in bacteria and pre-mRNA splicing or polyadenylation in eukaryotes. For all riboswitch classes examined, phylogenetic sequence analyses delineate a segment of highly conserved sequence that is necessary and sufficient for specific in vitro binding to their cognate metabolites. These specific binding domains, or aptamers, have been the central focus of studies investigating riboswitch mechanism and function. Conformational changes are thought to be an integral part of riboswitch function. Small angle X-ray scattering is a technique to probe the global nature of such conformational changes. Recently, several labs have published papers utilizing this technique to understand the metabolite-induced structural response of several riboswitch RNA. The current proposal is related to GUP12457 and GUP11627, both entitled "Investigating the proposed 'switching' mechanism of various riboswitches". The previous GUPs, for which beamtime was allocated, focused on examining the proposed general features of riboswitch function. SAXS analyses revealed idiosyncratic responses of various riboswitches to their respective small-molecule effectors as described in our recent publications (Baird and Ferre-D'Amare, RNA, 2010; Kulshina et al, NSMB, 2009).