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.
Heinz
Uwe
U
Department of Basic Sciences and Environment, Faculty of Life Sciences University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
Hemmingsen
Lars
L
Kiefer
Martin
M
Adolph
Hans-Werner
HW
D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry; D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D008667:Metalloproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers
D008667:Metalloproteins; D001224:Aspartic Acid; D018698:Glutamic Acid; D006639:Histidine; D015032:Zinc; D003545:Cysteine