Structural basis for guanidine sensing by the ykkC family of riboswitches.
Structural basis for guanidine sensing by the ykkC family of riboswitches.
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DOI：
10.1261/rna.060186.116
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Ke A
中科院分区：
文献类型：
--
作者：
Battaglia RA;Price IR;Ke A
通过顺式核糖开关调控基因表达是细菌中普遍存在的主题。在鉴定的数百个核糖开关家族中，大多数仍然是孤儿，没有明确的配体分配。ykkC孤儿家族最近被表征为胍敏感核糖开关。在此，我们提出了一个2.3 μ m的晶体结构的胍结合ykkC核糖开关从Dickeya dadantii。核糖开关折叠成靴形结构，同轴堆叠的P1/P2茎形成靴子，3′-P3茎环形成脚跟。复杂的碱基配对和交叉螺旋三级接触产生了靴子和鞋跟之间的配体结合口袋。通过共面氢键网络和保守鸟苷残基顶部的阳离子-π堆积接触，以其sp2杂交状态的带正电的胍形式识别胍。中断这些接触导致严重的胍结合缺陷。这些结果提供了特定的胍感测ykkC核糖开关的结构基础，并铺平了道路，更深入地了解胍解毒细菌生理学的一个以前不受重视的方面。
Regulation of gene expression by cis-encoded riboswitches is a prevalent theme in bacteria. Of the hundreds of riboswitch families identified, the majority of them remain as orphans, without a clear ligand assignment. The ykkC orphan family was recently characterized as guanidine-sensing riboswitches. Herein we present a 2.3 Å crystal structure of the guanidine-bound ykkC riboswitch from Dickeya dadantii. The riboswitch folds into a boot-shaped structure, with a coaxially stacked P1/P2 stem forming the boot, and a 3′-P3 stem–loop forming the heel. Sophisticated base-pairing and cross-helix tertiary contacts give rise to the ligand-binding pocket between the boot and the heel. The guanidine is recognized in its positively charged guanidinium form, in its sp2 hybridization state, through a network of coplanar hydrogen bonds and by a cation–π stacking contact on top of a conserved guanosine residue. Disruption of these contacts resulted in severe guanidinium-binding defects. These results provide the structural basis for specific guanidine sensing by ykkC riboswitches and pave the way for a deeper understanding of guanidine detoxification—a previously unappreciated aspect of bacterial physiology.