![Show Menu](styles/mobile-menu.png)
![Page Background](./../common/page-substrates/page0090.jpg)
Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
85
59-POS
Board 59
The Dynamic Behavior of the P2X4 Ion Channel in the Closed Conformation
Gustavo Pierdominici Sottile
2
, Agustin Ormazàbal
2
, Luciano Moffatt
3
, Juliana Palma
2
.
1
n/a, Bernal, Florida, Argentina,
2
Univesidad de Quilmes, Bernal, Argentina,
3
Universidad de
Buenos Aires, Buenos Aires, Argentina.
P2X receptors are a family of cationic channels whose opening is triggered by the binding of
ATP to the extracellular domain. They are widespread in the tissues of mammals and have a
broad range of functions. Due to this fact, an extensive number of investigations were leaded to
explain how they work. In spite of these efforts, many aspects of its functioning remain unclear.
One of them corresponds to understand how the closed-to-open transition takes place at a
molecular level. Since both (closed and open) conformations of P2X4 have been disclosed when
the crystallographic structures were obtained, this constitutes an ideal framework to perform
molecular dynamic simulations aimed to get insight into the movements of the system related to
the transition.
We will present the results of a detailed molecular dynamics study of the closed form of the
P2X4 receptor. The movement of the system were decomposed into inter-chain motions and
intra-chain deformations and were compared with the changes that occur in the transition from
the closed to the open structure. The analysis revealed that the expansion of the transmembrane
helices mainly results from inter-chain motions that already take place in the closed
conformation. However, they cannot reach the required amplitude because they are impeded by
interactions occurring around the ATP binding pocket. This suggests that the binding of ATP
would produce distortions in the chains that eliminate the restrictions on the inter-chain
displacements, leading to the opening of the pore. This knowledge not only could contribute to
learn about the general mechanisms of how these channels function but also could eventually
facilitate the development of potent inhibitors.