B12 cofactors directly stabilize an mRNA regulatory switch.
B12 cofactors directly stabilize an mRNA regulatory switch.
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与效应物结合的核糖开关受体结构域的结构揭示了信使核糖核酸（mRNA）如何识别多种小分子，但关于其与基因表达调控的关联机制细节仍然难以捉摸。为了解决这个问题，我们解析了两类不同的钴胺素（维生素B12）结合核糖开关的晶体结构，其中包括下游调控结构域的结构转换部分。这两类核糖开关具有一个共同的钴胺素结合核心，但利用不同的周边延伸来识别不同的B12衍生物。在每种情况下，识别是通过RNA和钴胺素之间的形状互补实现的，只有相对较少的通常控制RNA - 小分子识别的氢键相互作用。我们表明，一个复合的钴胺素/RNA支架稳定了一种不寻常的长距离分子内吻环相互作用，这种相互作用控制着mRNA的表达。这是第一个详细说明受体结构域和调控结构域如何以配体依赖的方式相互作用以调控mRNA表达的核糖开关晶体结构。
Structures of riboswitch receptor domains bound to their effector have revealed how mRNAs recognize diverse small molecules, but mechanistic details into its linkage with regulation of gene expression remain elusive. To address this, we solved crystal structures of two different classes of cobalamin (vitamin B12) binding riboswitches that include the structural switch of the downstream regulatory domain. These classes share a common cobalamin-binding core, but use distinct peripheral extensions to recognize different B12 derivatives. In each case, recognition is accomplished through shape complementarity between the RNA and cobalamin with relatively few hydrogen bonding interactions that typically govern RNA-small molecule recognition. We show that a composite cobalamin/RNA scaffold stabilizes an unusual long-range intramolecular kissing-loop interaction that controls mRNA expression. This is the first riboswitch crystal structure detailing how the receptor and regulatory domains communicate in a ligand-dependent fashion to regulate mRNA expression.