Shandong Key Laboratory of Biophysics, Dezhou University, Dezhou, 253023, China.
Department of Chemistry, University of Illinois Chicago, Chicago, IL, 60607, USA.
Commun Biol. 2023 Jul 31;6(1):791. doi: 10.1038/s42003-023-05175-5.
The SAM/SAH riboswitch binds S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) with similar affinities. Mg is generally known to stabilize RNA structures by neutralizing phosphates, but how it contributes to ligand binding and conformational transition is understudied. Here, extensive molecular dynamics simulations (totaling 120 μs) predicted over 10 inner-shell Mg ions in the SAM/SAH riboswitch. Six of them line the two sides of a groove to widen it and thereby pre-organize the riboswitch for ligand entry. They also form outer-shell coordination with the ligands and stabilize an RNA-ligand hydrogen bond, which effectively diminishes the selectivity between SAM and SAH. One Mg ion unique to the apo form maintains the Shine-Dalgarno sequence in an autonomous mode and thereby facilitates its release for ribosome binding. Mg thus plays vital roles in SAM/SAH riboswitch function.
SAM/SAH 核糖开关以相似的亲和力结合 S-腺苷甲硫氨酸 (SAM) 和 S-腺苷同型半胱氨酸 (SAH)。Mg 通常通过中和磷酸根来稳定 RNA 结构，但它如何促进配体结合和构象转变还研究得不够充分。在这里，通过广泛的分子动力学模拟（总计 120μs）预测了 SAM/SAH 核糖开关中有超过 10 个内壳层 Mg 离子。其中 6 个位于一个沟槽的两侧，以扩大其宽度，从而为配体进入预先组织核糖开关。它们还与配体形成外壳配位，并稳定 RNA-配体氢键，这有效地降低了 SAM 和 SAH 之间的选择性。一个独特的 apo 形式的 Mg 离子维持 Shine-Dalgarno 序列处于自主模式，从而促进其释放以进行核糖体结合。因此，Mg 在 SAM/SAH 核糖开关功能中发挥着至关重要的作用。
