Jones Christopher P, Ferré-D'Amaré Adrian R
Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Nat Struct Mol Biol. 2015 Sep;22(9):679-85. doi: 10.1038/nsmb.3073. Epub 2015 Aug 17.
The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. We report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg(2+) ion. We show that the affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. The ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression.
细菌警报素5-氨基咪唑-4-甲酰胺核苷5'-三磷酸（AICAR三磷酸或ZTP），由单磷酸化嘌呤前体ZMP衍生而来，在叶酸饥饿期间积累。ZTP通过一个同源核糖开关调节参与嘌呤和叶酸代谢的基因。连接该核糖开关两个亚结构域的接头长度变化超过100个核苷酸。我们报道了与ZMP结合的溃疡梭杆菌核糖开关的共晶体结构，它跨越两个亚结构域，其界面还包括一个假结和核糖拉链。该核糖开关通过与Mg(2+)离子前所未有的内球配位识别ZMP的甲酰胺氧。我们表明，核糖开关对ZMP的亲和力受接头长度调节。值得注意的是，即使两个亚结构域作为单独的RNA合成，ZMP也能同时与它们结合。ZTP核糖开关展示了特定小分子结合如何驱动远距离非编码RNA结构域的缔合以调节基因表达。
