3 / 23
Page 145
Notes:
conferenceseries
.com
Volume 10, Issue 8 (Suppl)
J Proteomics Bioinform, an open access journal
ISSN: 0974-276X
Structural Biology 2017
September 18-20, 2017
9
th
International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
Two distinct mechanisms of transcriptional regulation by the redox-sensor YodB
Sang Jae Lee
Seoul National University, Republic of Korea
F
or bacteria, cysteine thiol groups in proteins are commonly used as thiol-based switches for redox sensing to activate
specific detoxification pathways and restore the redox balance. Among the known thiol-based regulatory systems, the
MarR/DUF24 family regulators have been reported to sense and respond to reactive electrophilic species, including diamide,
quinones, and aldehydes, with high specificity. We report that the prototypical regulator YodB of the MarR/DUF24 family
from
Bacillus subtilis
utilizes two distinct pathways to regulate transcription in response to two reactive electrophilic species
(diamide or methyl-p-benzoquinone), as revealed by X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy,
and biochemical experiments. Diamide induces structural changes in the YodB dimer by promoting the formation of disulfide
bonds, whereas methyl-p-benzoquinone allows the YodB dimer to be dissociated from DNA, with little effect on the YodB
dimer. The results indicate that
B. subtilis
may discriminate toxic quinones, such as methyl-p-benzoquinone, from diamide to
efficiently manage multiple oxidative signals. This is the first evidence that different thiol reactive compounds induce dissimilar
conformational changes in the regulator to trigger the separate regulation of target DNA. This specific control of YodB is
dependent upon the type of thiol reactive compound present, is linked to its direct transcriptional activity, and is important for
the survival of
B. subtilis
. This study of
B. subtilis
YodB also provides a structural basis for the relationship that exists between
the ligand-induced conformational changes adopted by the protein and its functional switch.
Biography
Sang Jae Lee has his expertise in Structural Biology and Structure-Based Drug Discovery. His research interests span a wide range of topics in pathogenesis
of pathogenic bacteria including
Mycobacteria tuberculosis, Salmonella typhimurium
, human cholesterol metabolism, and human rare genetic diseases. Now he
works at the Research Institute of Pharmaceutical Sciences, Seoul National University.
sjlee@snu.ac.krSang Jae Lee, J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0101
Figure1:
Proposed redox switch mechanism for B.
subtilis YodB. The two pathways of the YodB protein
are depicted as (1) the diamide-mediated signaling
pathway and (2) quinone-mediated S-alkylation, with
each possible intermediate form.