PROTEOMIC ANALYSIS OF BIOMARKERS AND MECHANISMS OF TOXIC METAL STRESS

University Of California, San Francisco, San Francisco CA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this project, we are using a mass spectrometry proteomics approach to identify the cellular effects of exposure to Hg(II) and organomercurials. The initial project involves studies of E. coli cells that do or do not harbor a plasmid that carries the mer operon which encodes a bacterial mercury detoxification pathway. We have hypothesized that there may be two types of protein modifications resulting from exposure to the Hg compounds, (1) formation of Hg(II) and RHg(I) adducts with protein thiols, and (2) oxidiative modifications that may result if initial targets of Hg interaction stimulate formation of reactive oxygen species. One fairly straightforward aspect of work in my lab is to use a structure-based approach to build predictions of expected Hg(II)-dithiol and RHg(I)-thiol complexes of proteins to augment the databases used to identify modified peptides found in the mass spec analyses. The second aspect that has proved more important is to develop software tools to automate the analysis of the mass spec data to look for Hg-containing adducts and identify the peptides/proteins. While the second aspect does not really require use of Chimera, the first aspect does and further analysis of identified targets is anticipated to involve visualization of protein structures or homology models.