Trivalent arsenic inhibits the functions of chaperonin complex

Xuewen Pan, Stefanie Reissman, Nick R. Douglas, Zhiwei Huang, Daniel S. Yuan, Xiaoling Wang, J. Michael McCaffery, Judith Frydman, Jef D. Boeke

Research output: Contribution to journalArticlepeer-review

Abstract

The exact molecular mechanisms by which the environmental pollutant arsenic works in biological systems are not completely understood. Using an unbiased chemogenomics approach in Saccharomyces cerevisiae, we found that mutants of the chaperonin complex TRiC and the functionally related prefoldin complex are all hypersensitive to arsenic compared to a wild-type strain. In contrast, mutants with impaired ribosome functions were highly arsenic resistant. These observations led us to hypothesize that arsenic might inhibit TRiC function, required for folding of actin, tubulin, and other proteins postsynthesis. Consistent with this hypothesis, we found that arsenic treatment distorted morphology of both actin and microtubule filaments. Moreover, arsenic impaired substrate folding by both bovine and archaeal TRiC complexes in vitro. These results together indicate that TRiC is a conserved target of arsenic inhibition in various biological systems.

Original languageEnglish (US)
Pages (from-to)725-734
Number of pages10
JournalGenetics
Volume186
Issue number2
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Genetics

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