Structural insights into amino acid binding and gene control by a lysine riboswitch.
Structural insights into amino acid binding and gene control by a lysine riboswitch.
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DOI：
10.1038/nature07326
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发表时间：
2008-10-30
期刊：
影响因子：
64.8
通讯作者：
Patel, Dinshaw J.
中科院分区：
文献类型：
--
作者：
Serganov, Alexander;Huang, Lili;Patel, Dinshaw J.
在细菌中，几种氨基酸的细胞内浓度由核糖开关控制。重要的调节回路之一涉及赖氨酸特异性核糖开关，它指导赖氨酸以及赖氨酸和其他氨基酸常见前体的生物合成和运输。为了了解核糖开关识别氨基酸的分子基础，我们在此展示了海栖热袍菌赖氨酸核糖开关的 174 个核苷酸传感结构域在赖氨酸结合 (1.9 埃) 和游离 (3.1 埃) 状态下的晶体结构。核糖开关具有不寻常且复杂的结构，包括通过紧凑的五螺旋连接点连接的三螺旋和二螺旋束，并通过各种长程三级相互作用来稳定。赖氨酸与核糖开关的连接核心相互作用，并通过细长结合袋内的形状互补性以及通过与其带电末端的几个直接和 K+ 介导的氢键被特异性识别。我们的结构和生化研究表明核糖开关支架的预形成，并确定与稳定赖氨酸结合状态形成相关的构象变化，这防止核糖开关的选择性折叠并促进下游调节元件的形成。我们还确定了与不同赖氨酸类似物（包括抗生素）结合的核糖开关的几种结构，以努力了解赖氨酸核糖开关的配体结合能力并了解抗生素耐药性的本质。我们的结果在分子水平上提供了对赖氨酸核糖开关依赖性基因控制机制的见解，从而有助于继续努力探索核糖开关的制药和生物技术潜力。
In bacteria, the intracellular concentration of several amino acids is controlled by riboswitches. One of the important regulatory circuits involves lysine-specific riboswitches, which direct the biosynthesis and transport of lysine and precursors common for lysine and other amino acids. To understand the molecular basis of amino acid recognition by riboswitches, here we present the crystal structure of the 174-nucleotide sensing domain of the Thermotoga maritima lysine riboswitch in the lysine-bound (1.9 ångström (Å)) and free (3.1 Å) states. The riboswitch features an unusual and intricate architecture, involving three-helical and two-helical bundles connected by a compact five-helical junction and stabilized by various long-range tertiary interactions. Lysine interacts with the junctional core of the riboswitch and is specifically recognized through shape-complementarity within the elongated binding pocket and through several direct and K+-mediated hydrogen bonds to its charged ends. Our structural and biochemical studies indicate preformation of the riboswitch scaffold and identify conformational changes associated with the formation of a stable lysine-bound state, which prevents alternative folding of the riboswitch and facilitates formation of downstream regulatory elements. We have also determined several structures of the riboswitch bound to different lysine analogues, including antibiotics, in an effort to understand the ligandbinding capabilities of the lysine riboswitch and understand the nature of antibiotic resistance. Our results provide insights into a mechanism of lysine-riboswitch-dependent gene control at the molecular level, thereby contributing to continuing efforts at exploration of the pharmaceutical and biotechnological potential of riboswitches.
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影响因子：
--
作者：
Serganov, A;Yuan, YR;Patel, DJ
通讯作者：
Patel, DJ
DOI：
10.1038/8263
发表时间：
1999-05-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Perrakis, A;Morris, R;Lamzin, VS
通讯作者：
Lamzin, VS
影响因子：
64.8
作者：
Batey, RT;Gilbert, SD;Montange, RK
通讯作者：
Montange, RK
影响因子：
56.9
作者：
Klein, Daniel J.;Ferre-D'Amare, Adrian R.
通讯作者：
Ferre-D'Amare, Adrian R.
影响因子：
5.7
作者：
Edwards, Thomas E.;Ferre-D'Amare, Adrian R.
通讯作者：
Ferre-D'Amare, Adrian R.