O'Keeffe, Grainne and Jöchl, Christoph and Kavanagh, Kevin and Doyle, Sean
(2013)
Extensive proteomic remodeling is
induced by eukaryotic translation
elongation factor 1Bc deletion in
Aspergillus fumigatus.
Protein Science, 22 (11).
pp. 1612-1622.
ISSN 0961-8368
Abstract
The opportunistic pathogen Aspergillus fumigatus is ubiquitous in the environment and
predominantly infects immunocompromised patients. The functions of many genes remain unknown
despite sequencing of the fungal genome. A putative translation elongation factor 1Bc (eEF1Bc,
termed elfA; 750 bp) is expressed, and exhibits glutathione S-transferase activity, in A. fumigatus.
Here, we demonstrate the role of ElfA in the oxidative stress response, as well as a possible involvement
in translation and actin cytoskeleton organization, respectively. Comparative proteomics, in
addition to phenotypic analysis, under basal and oxidative stress conditions, demonstrated a role for
A. fumigatus elfA in the oxidative stress response. An elfA-deficient strain (A. fumigatus DelfA) was
significantly more sensitive to the oxidants H2O2, diamide, and 4,40-dipyridyl disulfide (DPS) than the
wild-type. This was further supported with the identification of differentially expressed proteins of
the oxidative stress response, including; mitochondrial peroxiredoxin Prx1, molecular chaperone
Hsp70 and mitochondrial glycerol-3-phosphate dehydrogenase. Phenotypic analysis also revealed
that A. fumigatus DelfA was significantly more tolerant to voriconazole than the wild-type. The differential
expression of two aminoacyl-tRNA synthetases suggests a role for A. fumigatus elfA in translation,
while the identification of actin-bundling protein Sac6 and vacuolar dynamin-like GTPase
VpsA link A. fumigatus elfA to the actin cytoskeleton. Overall, this work highlights the diverse roles
of A. fumigatus elfA, with respect to translation, oxidative stress and actin cytoskeleton organization.
In addition to this, the strategy of combining targeted gene deletion with comparative proteomics
for elucidating the role of proteins of unknown function is further revealed.
| Item Type: |
Article
|
| Additional Information: |
The definitive published version of this article is available at DOI: 10.1002/pro.2367 |
| Keywords: |
proteomics; translation; GST; redox; elongation factor; glutathione; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
6894 |
| Identification Number: |
https://doi.org/10.1002/pro.2367 |
| Depositing User: |
Dr. Kevin Kavanagh
|
| Date Deposited: |
20 Jan 2016 13:20 |
| Journal or Publication Title: |
Protein Science |
| Publisher: |
Wiley Blackwell |
| Refereed: |
Yes |
| Funders: |
Irish Research Council for Science Engineering and Technology (IRCSET), Higher Education Authority (HEA), Science Foundation Ireland (SFI) |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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