Insights into metalloregulation by M-box riboswitch RNAs via structural analysis of manganese-bound complexes.
Insights into metalloregulation by M-box riboswitch RNAs via structural analysis of manganese-bound complexes.
复制标题
DOI：
10.1016/j.jmb.2011.01.049
复制
发表时间：
2011-04-08
影响因子：
5.6
通讯作者：
Winkler WC
中科院分区：
文献类型：
--
作者：
Ramesh A;Wakeman CA;Winkler WC
M-box核糖开关将细胞内镁水平与细菌金属运输基因的表达联系起来。对其他核糖开关RNA类别的结构分析表明，配体识别是通过碱基堆积、静电和氢键相互作用发生的。相反，M-box RNA在与一组未定义的金属结合时会触发基因表达的变化，而不是只对单一配体做出反应。先前的生物物理实验表明，二价离子与M-box RNA结合促进了紧凑的三级构象，导致了下游基因表达所需的短序列链的隔离。对于松散结合的金属的静电屏蔽无疑是金属介导的压实过程中的一个重要影响因素。然而，二价离子的子集也可能专门占据阳离子结合部位，并促进官能团的正确定位，以实现三级结构的稳定。为了更好地阐明这些金属结合位点的作用，用X射线结晶学方法将锰与M-box RNA的络合物分解为1.86埃。这些数据支持至少8个有序的阳离子结合口袋的存在，包括几个生化研究预测但在之前的结构分析中没有观察到的位点。总体而言，这些数据支持M-box RNA中存在三个金属结合核心，这三个核心促进了金属结合、紧凑构象中的远程相互作用网络。
The M-box riboswitch couples intracellular magnesium levels to expression of bacterial metal transport genes. Structural analyses of other riboswitch RNA classes, which typically respond to a small organic metabolite, have revealed that ligand recognition occurs through a combination of base stacking, electrostatic, and hydrogen bonding interactions. In contrast, the M-box RNA triggers a change in gene expression upon association with an undefined population of metals, rather than responding to only a single ligand. Prior biophysical experimentation suggested that divalent ions associate with the M-box RNA to promote a compacted tertiary conformation, resulting in sequestration of a short sequence tract otherwise required for downstream gene expression. Electrostatic shielding from loosely associated metals is undoubtedly an important influence during this metal-mediated compaction pathway. However, it is also likely that a subset of divalent ions specifically occupies cation-binding sites and promotes proper positioning of functional groups for tertiary structure stabilization. To better elucidate the role of these metal-binding sites a manganese-chelated M-box RNA complex was resolved to 1.86 angstroms by X-ray crystallography. These data support the presence of at least 8 well-ordered cation binding pockets, including several sites that had been predicted by biochemical studies but were not observed in prior structural analysis. Overall, these data support the presence of three metal binding cores within the M-box RNA that facilitate a network of long range interactions within the metal-bound, compacted conformation.
登录
查看更多内容
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.9
作者：
Ennifar, E;Walter, P;Dumas, P
通讯作者：
Dumas, P
影响因子：
5.4
作者：
Dambach, Michael D.;Winkler, Wade C.
通讯作者：
Winkler, Wade C.
DOI：
10.1038/nsb0797-553
发表时间：
1997-07-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Cate, JH;Hanna, RL;Doudna, JA
通讯作者：
Doudna, JA
影响因子：
16.6
作者：
Forconi, Marcello;Sengupta, Raghuvir N.;Herschlag, Daniel
通讯作者：
Herschlag, Daniel