Nonlocal Helix Formation Is Key to Understanding S-Adenosylmethionine-1 Riboswitch Function
Nonlocal Helix Formation Is Key to Understanding S-Adenosylmethionine-1 Riboswitch Function
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DOI：
10.1016/j.bpj.2008.10.033
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发表时间：
2009-01-21
影响因子：
3.4
通讯作者：
Sanbonmatsu, Kevin Y.
中科院分区：
文献类型：
--
作者：
Whitford, Paul C.;Schug, Alexander;Sanbonmatsu, Kevin Y.
核糖开关是非编码RNA，其响应于特定代谢物的浓度变化而调节基因表达。转换活性受到核糖开关的适体结构域和表达平台之间的相互作用的影响。适体结构域结合代谢物，将核糖开关锁定在配体结合构象中。在不存在代谢物的情况下，表达平台通过隔离称为P1的非局部螺旋的3'末端形成替代二级结构。我们使用基于全原子结构的模拟来表征S-腺苷甲硫氨酸-1（SAM-1）核糖开关的适体结构域的折叠、展开和代谢物结合。我们的研究结果表明，折叠的非本地螺旋（P1）是适体结构域形成的限速。有趣的是，SAM通过降低相关的自由能垒来帮助P1螺旋的折叠。由于P1螺旋的3'末端在不存在代谢物的情况下被替代螺旋隔离，因此观察到的P1形成的配体控制提供了表达平台调控的机制解释。
Riboswitches are noncoding RNAs that regulate gene expression in response to changing concentrations of specific metabolites. Switching activity is affected by the interplay between the aptamer domain and expression platform of the riboswitch. The aptamer domain binds the metabolite, locking the riboswitch in a ligand-bound conformation. In absence of the metabolite, the expression platform forms an alternative secondary structure by sequestering the 3' end of a nonlocal helix called P1. We use all-atom structure-based simulations to characterize the folding, unfolding, and metabolite binding of the aptamer domain of the S-adenosylmethionine-1 (SAM-1) riboswitch. Our results suggest that folding of the nonlocal helix (P1) is rate-limiting in aptamer domain formation. Interestingly, SAM assists folding of the P1 helix by reducing the associated free energy barrier. Because the 3' end of the P1 helix is sequestered by an alternative helix in the absence of metabolites, this observed ligand-control of P1 formation provides a mechanistic explanation of expression platform regulation.