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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
Ivan Barvik et al., J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0101
Mechanism for PIP2 activation of TRP channels
Ivan Barvik
and
Vlastimil Zima
Charles University, Czech Republic
T
ransient receptor potential (TRP)-related channels are a large, diverse superfamily of proteins consisting of up to 28
members in mammals (1). TRP channels are activated by diverse cellular and environmental signals. Inhibition of TRP
channels expressed on nociceptive neurons represents a viable therapeutic pain target (2-3). The recent high-resolution
structures captured TRP channels in different conformations (4-5). All TRP channels form functional tetramers, with each
subunit consisting of six transmembrane segments (S1-S6) flanked by amino- and carboxyl-terminal cytosolic domains. The
S1-S4 helices form isolated sensor domains arranged radially around the periphery of the central-ion conducting pore, which is
lined with four S5-S6 domains. The central cavity involved in the ion permeation exhibits major constrictions at the selectivity
filter, as well as at the lower gate. The proximal C-terminal region represents the only cytosolic region of sequence conserved
among TRP channels. This region can be divided into three sections: the six-amino acid TRP box; a variable region, historically
known as the “TRP domain”; and a poly-basic region proposed that constitutes the PIP2 binding site (6-7). The putative PIP2
binding region contains three to nine positively charged amino acids and, typically, one or more aromatic amino acids (7). Here,
we use bioinformatics tools, sequence and structural alignments, homology modeling and molecular dynamics simulations
to propose a detail molecular mechanism, how TRP channels are activated by PIP2. We describe pathways through which the
signal is transmitted from peripheral binding sites of PIP2 up to the lower gate of TRP channels. Evolutionary conserved amino
acids that serve as key switches during transitions between closed and open states of TRP channels are identified.
Biography
Ivan Barvík is now the Assistant Professor at the Institute of Physics of Charles University. He is interested in computer modeling of biomolecules (bioinformatics,
homology modeling, molecular docking, rational drug design, molecular dynamics simulations, quantum chemical calculations), high performance computing &
parallelization (OpenMP, MPI, CUDA) and numerical methods.
ibarvik@karlov.mff.cuni.cz