Heavy metal ions are potent inhibitors of protein folding
- Biochemisches Institut, Universitaet Zuerich, CH-8057 Zuerich (Switzerland)
- Departement de Biologie Moleculaire Vegetale, Universite de Lausanne, CH-1015 Lausanne (Switzerland)
Environmental and occupational exposure to heavy metals such as cadmium, mercury and lead results in severe health hazards including prenatal and developmental defects. The deleterious effects of heavy metal ions have hitherto been attributed to their interactions with specific, particularly susceptible native proteins. Here, we report an as yet undescribed mode of heavy metal toxicity. Cd{sup 2+}, Hg{sup 2+} and Pb{sup 2+} proved to inhibit very efficiently the spontaneous refolding of chemically denatured proteins by forming high-affinity multidentate complexes with thiol and other functional groups (IC{sub 50} in the nanomolar range). With similar efficacy, the heavy metal ions inhibited the chaperone-assisted refolding of chemically denatured and heat-denatured proteins. Thus, the toxic effects of heavy metal ions may result as well from their interaction with the more readily accessible functional groups of proteins in nascent and other non-native form. The toxic scope of heavy metals seems to be substantially larger than assumed so far.
- OSTI ID:
- 21143783
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 372, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.05.052; PII: S0006-291X(08)00952-2; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Protein structure prediction and potential energy landscape analysis using continuous global minimization
High mobility group protein DSP1 negatively regulates HSP70 transcription in Crassostrea hongkongensis