Structural Adaptability of Zinc Binding Sites: Different Structures in Partially, Fully, and Heavy-Metal Loaded States

The present study demonstrates that both the nature (Zn-II, Cd-II or Hg-II) and supply of metal ions determine Whether Zinc fingers fold into the well-known, fully loaded structures or alternatively populate a variety of structural states under substoichiometric conditions. Metal-bridged species are observed by perturbed angular correlation (PAC), EXAFS, UV spectroscopy, and stopped-flow kinetics. Transitions between structural states as adaptive reactions to changed metal-ion supply might represent intelligent system changes in zinc homeostasis, trafficking and signalling, and reflect features of heavy-metal toxicity at the molecular level. Because the zinc fingers exist in structural states that are different from the metal-free and fully loaded species, the prevailing view on metal-mediated molecular regulation in terms of on and off control might be oversimplified.