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.