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RNA Topology as a Framework for Structure, Dynamics and Adaptation.
[摘要] The thermodynamic rules that link RNA sequences to secondary structure are well established while the link between its secondary structure and three-dimensional global conformation remains poorly understood. A-form helices – which represent ~50% of all RNA secondary structural elements in the PDB – are the most common secondary structural element of RNA. In fact, the global conformation and shape of RNA is largely defined by the relative arrangement of A-form helices linked by flexible pivot points. Of these flexible pivots, approximately 70% consist of two-way junctions such as bulges and internal loops. We have constructed comprehensive three-dimensional cubic maps depicting the relative orientation of A-form helices across RNA junctions as collected from the Protein Data Bank, and rationalized the findings using modeling and NMR spectroscopy. First, we derive a new angular nomenclature that utilized Euler angles to measure and describe the relative orientation of two helices. Next, we show that the secondary structure of junctions code for readily computable topological constraints that accurately predict the three-dimensional orientation of helices across all two-way junctions. And Finally, we rationalize adaptive changes that occur upon ligand binding in terms of the conformational orientations available to different junctions. The results herein suggest that the global conformation and orientation of helices is largely defined by topological constraints encoded within RNA’s secondary structure, and that tertiary contacts, along with other intermolecular interactions, act to stabilize specific structures from within a larger continuum of available topologically allowed conformers. Results from this work have the potential to enhance the development of applications in biotechnology and the targeting and development of therapeutics, as well as expand our understanding of RNA folding, and disordered RNA conformers in general (e.g. riboswitches). Additionally, there are a number of direct applications of this work that will readily impact the field of RNA structure prediction and modeling. This research will have a direct impact on our understanding of the role of structural dynamics and conformational adaptation within biology at large.
[发布日期]  [发布机构] University of Michigan
[效力级别] Chemistry [学科分类] 
[关键词] RNA Topology;Chemistry;Science;Chemistry [时效性] 
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