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Title: Heavy metal ions are potent inhibitors of protein folding

Abstract

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.

Authors:
 [1];  [2];  [1]
  1. Biochemisches Institut, Universitaet Zuerich, CH-8057 Zuerich (Switzerland)
  2. Departement de Biologie Moleculaire Vegetale, Universite de Lausanne, CH-1015 Lausanne (Switzerland)
Publication Date:
OSTI Identifier:
21143783
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 372; Journal 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); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CADMIUM; CADMIUM IONS; HEALTH HAZARDS; HEAVY METALS; LEAD; LEAD IONS; MERCURY; MERCURY IONS; OCCUPATIONAL EXPOSURE; PROTEINS; THIOLS; TOXICITY

Citation Formats

Sharma, Sandeep K, Departement de Biologie Moleculaire Vegetale, Universite de Lausanne, CH-1015 Lausanne, Goloubinoff, Pierre, and Christen, Philipp. Heavy metal ions are potent inhibitors of protein folding. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2008.05.052.
Sharma, Sandeep K, Departement de Biologie Moleculaire Vegetale, Universite de Lausanne, CH-1015 Lausanne, Goloubinoff, Pierre, & Christen, Philipp. Heavy metal ions are potent inhibitors of protein folding. United States. https://doi.org/10.1016/j.bbrc.2008.05.052
Sharma, Sandeep K, Departement de Biologie Moleculaire Vegetale, Universite de Lausanne, CH-1015 Lausanne, Goloubinoff, Pierre, and Christen, Philipp. 2008. "Heavy metal ions are potent inhibitors of protein folding". United States. https://doi.org/10.1016/j.bbrc.2008.05.052.
@article{osti_21143783,
title = {Heavy metal ions are potent inhibitors of protein folding},
author = {Sharma, Sandeep K and Departement de Biologie Moleculaire Vegetale, Universite de Lausanne, CH-1015 Lausanne and Goloubinoff, Pierre and Christen, Philipp},
abstractNote = {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.},
doi = {10.1016/j.bbrc.2008.05.052},
url = {https://www.osti.gov/biblio/21143783}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 372,
place = {United States},
year = {Fri Jul 25 00:00:00 EDT 2008},
month = {Fri Jul 25 00:00:00 EDT 2008}
}