Crystal structure of the effector-binding domain of the trehalose-repressor of Escherichia coli, a member of the LacI family, in its complexes with inducer trekalose-6-phosphate and noninducer trehalose
Crystal structure of the effector-binding domain of the trehalose-repressor of Escherichia coli, a member of the LacI family, in its complexes with inducer trekalose-6-phosphate and noninducer trehalose
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DOI：
10.1002/pro.5560071204
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发表时间：
1998-12-01
期刊：
影响因子：
8
通讯作者：
Diederichs, K
中科院分区：
文献类型：
--
作者：
Hars, U;Horlacher, R;Diederichs, K
用多重同晶置换法（MIR）测定了大肠杆菌海藻糖阻遏物（TreR）与其诱导剂海藻糖-6-磷酸复合物的晶体结构，然后用MIR测定了其与非诱导剂海藻糖复合物的晶体结构。该模型由残基61至315组成，其包含效应子结合结构域，其形成与LacI家族其他成员一样的二聚体。该结构域由两个相似的亚结构域组成，每个亚结构域由夹在α-螺旋之间的中心β-折叠组成。效应子结合口袋位于这些亚结构域的界面处。尽管不同的生理功能，TreR的两个复合物的晶体结构被证明是几乎相同的，彼此的构象是类似的效应器结合结构域的LacI和PurR的复合物与它们的效应分子。根据晶体结构，非诱导剂海藻糖与海藻糖-6-磷酸的海藻糖部分结合的位点相似。前者的结合亲和力低于后者。因此，非诱导剂海藻糖竞争性结合阻遏物。与磷酸化诱导分子不同，它不能阻断阻遏物头部与其操纵基因DNA的结合。因此，海藻糖-6-磷酸和海藻糖的浓度比用于在海藻糖作为微生物保护剂和作为碳源的两种替代代谢用途之间切换。
The crystal structure of the Escherichia coli trehalose repressor (TreR) in a complex with its inducer trehalose-6-phosphate was determined by the method of multiple isomorphous replacement (MIR) at 2.5 Angstrom resolution, followed by the structure determination of TreR in a complex with its noninducer trehalose at 3.1 Angstrom resolution. The model consists of residues 61 to 315 comprising the effector binding domain, which forms a dimer as in other members of the LacI family. This domain is composed of two similar subdomains each consisting of a central beta-sheet sandwiched between alpha-helices. The effector binding pocket is at the interface of these subdomains. In spite of different physiological functions, the crystal structures of the two complexes of TreR turned out to be virtually identical to each other with the conformation being similar to those of the effector binding domains of the LacI and PurR in complex with their effector molecules. According to the crystal structure, the noninducer trehalose binds to a similar site as the trehalose portion of trehalose-6-phosphate. The binding affinity for the former is lower than for the latter. The noninducer trehalose thus binds competitively to the repressor. Unlike the phosphorylated inducer molecule, it is incapable of blocking the binding of the repressor headpiece to its operator DNA. The ratio of the concentrations of trehalose-6-phosphate and trehalose thus is used to switch between the two alternative metabolic uses of trehalose as an osmoprotectant and as a carbon source.