The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR
The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR
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DOI：
10.1093/emboj/20.8.2041
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发表时间：
2001-04-17
期刊：
影响因子：
11.4
通讯作者：
Knudsen, J
中科院分区：
文献类型：
--
作者：
van Aalten, DMF;Dirusso, CC;Knudsen, J
FadR是一种酰基辅酶A反应性转录因子，在大肠杆菌中调节脂肪酸生物合成和降解基因，ape蛋白以同源二聚体的形式与DNA结合，这种相互作用被酰基辅酶A的结合所破坏。最近描述的apo-FadR的结构显示了一个DNA结合结构域与一个具有新折叠的酰基辅酶A结合结构域偶联，但没有解释酰基辅酶A效应分子在距离DNA结合位点> 30埃处的结合如何影响转录调节。在这里，我们描述的FadR-运营商和FadR-肉豆蔻酰辅酶A二元复合物的结构。FadR-DNA复合物揭示了一种新的有翼螺旋-转角-螺旋蛋白-DNA相互作用，涉及从翼到小沟的序列特异性接触。酰基-CoA的结合导致整个蛋白质的显著构象变化，主链移位高达4.5埃。净效应是二聚体中DNA结合结构域的重排，导致DNA识别螺旋分离的7.2埃变化和DNA结合的丧失，揭示了酰基-CoA响应性调节的分子基础。
FadR is an acyl-Coh-responsive transcription factor, regulating fatty acid biosynthetic and degradation genes in Escherichia coli, The ape-protein binds DNA as a homodimer, an interaction that is disrupted by binding of acyl-CoA, The recently described structure of apo-FadR shows a DNA binding domain coupled to an acyl-CoA binding domain with a novel fold, but does not explain how binding of the acyl-CoA effector molecule > 30 Angstrom away from the DNA binding site affects transcriptional regulation. Here, we describe the structures of the FadR-operator and FadR-myristoyl-CoA binary complexes. The FadR-DNA complex reveals a novel winged helix-turn-helix protein-DNA interaction, involving sequence-specific contacts from the wing to the minor groove. Binding of acyl-CoA results in dramatic conformational changes throughout the protein, with backbone shifts up to 4.5 Angstrom, The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 Angstrom in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.