Changela Anita, Chen Kui, Xue Yi, Holschen Jackie, Outten Caryn E, O'Halloran Thomas V, Mondragón Alfonso
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2205Tech Drive, Evanston, IL 60208, USA.
Science. 2003 Sep 5;301(5638):1383-7. doi: 10.1126/science.1085950.
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 +1transition-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.
大肠杆菌中一系列铜离子外排基因中最早的那些基因受CueR调控，CueR是转录激活因子MerR家族的一员。对CueR的热力学校准显示其对游离Cu+的灵敏度为zeptomolar（10的负21次方摩尔），这远低于每个细胞一个原子。通过比较CueR和锌离子感应同源物ZntR的晶体结构，揭示了这种对 +1 过渡金属离子的非凡灵敏度和选择性的原子细节。CueR中一个不同寻常的埋藏金属受体位点将金属限制在直线型、双配位几何结构中，并利用螺旋偶极和氢键相互作用增强金属结合。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。
