Yonghui Chen
Kevin D. Reilly
Yongchang Chang
Evolutionary conserved allosteric network of
ligand-gated ion channels revealed by
sequence-based statistical method.
The 13th Annual International Conference on Intelligent Systems for Molecular Biology, 31, Detriot, June
Poster Presentation
ABSTRACT
Ligand-gated channels (LGICs) mediate fast synaptic
transmission for communication between neurons. These channels
are allosteric proteins, in which binding of a neurotransmitter to
its binding site in the extracellular amino-terminal domain triggers
structural changes in distant transmembrane domains to open a
channel for ion flow. To gain insight in the structural basis of this
long-range allosteric coupling, we analysed multiple sequences of
LGICs by adapting a previously developed statistical method as
well as a clustering analysis and a 3-D structural model. Statistical
coupling energy calculation along with clustering analysis revealed a
highly coupled cluster. Mapping the positions in this cluster onto a 3-D
structural model demonstrated that these highly coupled positions
were mainly clustered in previously identified important functional
domains for binding, coupling, and gating. Thus, our results revealed
a genetically interconnected network, which potentially plays an
important role in the allosteric activation of LGICs.
Key Words:
Evolutionary conservation, allosteric netwok, ligand-gated ion
channels, sequence statistics, clustering analysis, 3-D structural model.