Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR

Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR
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DOI:
10.1126/science.1085950
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发表时间:
2003-09-05
期刊:
影响因子:
56.9
通讯作者:
Mondragón, A
Mondragón, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Changela, A;Chen, K;Mondragón, A

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大肠杆菌中最早的一系列铜外排基因由CueR控制,CueR是MerR家族转录激活因子的成员。CueR的热力学校准揭示了对游离Cu+的zeptomolar(10(-21)摩尔)灵敏度,其远小于每个细胞一个原子。通过比较CueR和Zn 2+传感同系物ZntR的晶体结构,揭示了这种非凡的灵敏度和选择性的原子细节。一个不寻常的埋在CueR的金属受体网站限制金属的线性,两个坐标的几何形状,并使用螺旋偶极子和氢键相互作用,以提高金属结合。这种结合模式在金属蛋白中很少见,但非常适合作为超灵敏的遗传开关。
The earliest of a series of copper efflux genes in Escherichia coli are controlled by CueR, a member of the MerR family of transcriptional activators. Thermodynamic calibration of CueR reveals a zeptomolar (10(-21) molar) sensitivity to free Cu+, which is far less than one atom per cell. Atomic details of this extraordinary sensitivity and selectivity for +1 transition-metal ions are revealed by comparing the crystal structures of CueR and a Zn2+-sensing homolog, ZntR. An unusual buried metal-receptor site in CueR restricts the metal to a linear, two-coordinate geometry and uses helix-dipole and hydrogen-bonding interactions to enhance metal binding. This binding mode is rare among metalloproteins but well suited for an ultrasensitive genetic switch.