Cooperative and Directional Folding of the preQ1 Riboswitch Aptamer Domain
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- 作者：Jun Feng ; Nils G. Walter ; Charles L. Brooks ; III
- 刊名：Journal of the American Chemical Society
- 出版年：2011
- 出版时间：March 30, 2011
- 年：2011
- 卷：133
- 期：12
- 页码：4196-4199
- 全文大小：780K
- 年卷期：v.133,no.12(March 30, 2011)
- ISSN：1520-5126
文摘
Riboswitches are cis-acting RNA fragments that regulate gene expression by sensing cellular levels of the associated small metabolites. In bacteria, the class I preQ1 riboswitch allows the fine-tuning of queuosine biosynthesis in response to the intracellular concentration of the queuosine anabolic intermediate preQ1. When binding preQ1, the aptamer domain undergoes a significant degree of secondary and tertiary structural rearrangement and folds into an H-type pseudoknot. Conformational 鈥渟witching鈥?of the riboswitch aptamer domain upon recognizing its cognate metabolite plays a key role in the regulatory mechanism of the preQ1 riboswitch. We investigate the folding mechanism of the preQ1 riboswitch aptamer domain using all-atom Go虆-model simulations. The folding pathway of such a single domain is found to be cooperative and sequentially coordinated, as the folding proceeds in the 5鈥?鈫?3鈥?direction. This kinetically efficient folding mechanism suggests a fast ligand-binding response in competition with RNA elongation.