Structural basis for transcription regulation by alarmone ppGpp
Structural basis for transcription regulation by alarmone ppGpp
复制标题
DOI：
10.1016/s0092-8674(04)00401-5
复制
发表时间：
2004-04-30
期刊：
影响因子：
64.5
通讯作者：
Vassylyev, DG
中科院分区：
文献类型：
--
作者：
Artsimovitch, I;Patlan, V;Vassylyev, DG
鸟苷四磷酸（ppGpp）是严谨控制的主要调节因子，是细菌对氨基酸饥饿的一种适应性反应。嗜热栖热菌（Thermus thermophilus）RNA聚合酶（RNAP）全酶与ppGpp复合物的2.7埃分辨率结构显示，ppGpp在晶体中的两个独立RNAP分子的活性中心附近结合在相同位点，但取向明显不同。结合相对于ppGpp的两个二磷酸是对称的，而相对于核苷酸碱基的取向是宽松的。ppGpp结合的不同模式与活性位点构象的不对称相关。结果表明，ppGpp与非模板DNA链中的胞嘧啶碱基配对可能是ppGpp转录控制的一个重要组成部分。我们提供了实验证据，强调了在转录起始和延伸过程中ppGpp与特定胞嘧啶残基之间碱基特异性接触的重要性。
Guanosine-tetraphosphate (ppGpp) is a major regulator of stringent control, an adaptive response of bacteria to amino acid starvation. The 2.7 Angstrom resolution structure of the Thermus thermophilus RNA polymerase (RNAP) holoenzyme in complex with ppGpp reveals that ppGpp binds to the same site near the active center in both independent RNAP molecules in the crystal but in strikingly distinct orientations. Binding is symmetrical with respect to the two diphosphates of ppGpp and is relaxed with respect to the orientation of the nucleotide base. Different modes of ppGpp binding are coupled with asymmetry of the active site configurations. The results suggest that base pairing of ppGpp with cytosines in the nontemplate DNA strand might be an essential component of transcription control by ppGpp. We present experimental evidence highlighting the importance of base-specific contacts between ppGpp and specific cytosine residues during both transcription initiation and elongation.