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.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
Jianmin Cui, J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0100
PIP2 modulation of KCNQ1 channels
Jianmin Cui
Washington University in St. Louis, USA
V
oltage-gated ion channels generate dynamic ionic currents that are vital to the physiological functions of many tissues.
These proteins contain separate voltage-sensing domains, which detect changes in transmembrane voltage, and pore
domains, which conduct ions. Coupling of voltage sensing and pore opening is critical to the channel function and has been
modeled as a protein–protein interaction between the two domains. However, our data show that coupling in Kv7.1 channels
requires the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). We found that voltage-sensing domain activation failed to
open the pore in the absence of PIP2. This result is due to loss of coupling because PIP2 was also required for pore opening
to affect voltage-sensing domain activation. We identified a critical site for PIP2-dependent coupling at the interface between
the voltage-sensing domain and the pore domain. This site is a conserved lipid-binding site among different K+ channels,
suggesting that lipids play a significant role in coupling in many ion channels. To further investigate the mechanism of PIP2
mediated VSD-pore coupling, we identified a compound that mimics PIP2 structure and function as a molecular probe. This
compound was identified using an in-silico screening approach based on molecular docking of a library of compounds to
the PIP2 binding site in a homology model of the Kv7.1 channel. Our results show that this compound can substitute PIP2 in
activating the Kv7.1 channel.
Biography
Jianmin Cui is a Professor on the Spencer T. Olin Endowment at Washington University in St. Louis, in the Department of Biomedical Engineering. He received PhD
in Physiology and Biophysics from State University of New York at Stony Brook and a Post-Doctoral training at Stanford University. He was an assistant professor
of Biomedical Engineering at Case Western Reserve University before moving to St. Louis. His research interests include BK-type calcium-activated potassium
channels and IK
s
channels.
jcui@wustl.eduFigure1
. Kv7.1 activation depends on PIP2. Left. Kv7.1
currents in an inside-out patch decreases with time due to
PIP2 diffusion out of the membrane patch. Right. Cytosolic
PIP2 application (µM) activates Kv7.1.