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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
Su Youn Lee et al., J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0101
Structure-based dynamic diversity in regulatory domains of sodium calcium exchanger (NCX)
isoforms
Su Youn Lee
1
, Moshe Giladi
2
, Ka Young Chung
1
and
Daniel Khananshvili
2
1
Sungkyunkwan University, South Korea
2
Tel-Aviv University, Israel
M
ammalian Na
+
/Ca
2+
exchangers, NCX1 and NCX3, generate splice variants, whereas NCX2 does not. The CBD1 and
CBD2 domains form a regulatory tandem (CBD12), where Ca
2+
binding to CBD1 activates and Ca
2+
binding to CBD2
(bearing the splicing segment) alleviates the Na+-induced inactivation. Here, the NCX2-CBD12, NCX3-CBD12-B, and
NCX3-CBD12-AC proteins were analyzed by small-angle X-ray scattering (SAXS) and hydrogen-deuterium exchange mass-
spectrometry (HDX-MS) to resolve regulatory variances in the NCX2 and NCX3 variants. SAXS revealed the unified model,
according to which the Ca
2+
binding to CBD12 shifts a dynamic equilibrium without generating new conformational states,
and where more rigid conformational states become more populated without any global conformational changes. HDX-MS
revealed the differential effects of the B and AC exons on the folding stability of apo CBD1 in NCX3-CBD12, where the
dynamic differences become less noticeable in the Ca
2+
-bound state. Therefore, the apo forms predefine incremental changes in
backbone dynamics upon Ca
2+
binding. These observations may account for slower inactivation (caused by slower dissociation
of occluded Ca
2+
from CBD12) in the skeletal vs the brain-expressed NCX2 and NCX3 variants. This may have physiological
relevance, since NCX must extrude much higher amounts of Ca
2+
from the skeletal cell than from the neuron.
Biography
Su Youn Lee is currently studying the structures of drug-target proteins in her PhD program. She has been trained to study the structures of proteins using HDX-
MS, which provides information about the conformational change of proteins. She has collaborated with an expert in the NCX field and played a significant role
in a project which elaborated the dynamics and the structural mechanism of NCX regulation. And the results of this study have been published on major journals
(
Biochem J
2015
, FASEB J
2016, and
Scientific Reports
2017). Her study will contribute in suggesting a new NCX drug target sites, which will increase the
selectivity and effectiveness and reduce side effects of NCX targeting drugs.
youn3887@hanmail.net