The dynamic behavior of the P2X4 ion channel in the closed conformation

GUSTAVO PIERDOMINICI-SOTTILE; LUCIANO MOFFAT; JULIANA PALMA

BIOPHYSICAL JOURNAL

CELL PRESS

Lugar: United States; Año: 2016 vol. 111 p. 2642 - 2650

0006-3495

We present the results of a detailed molecular dynamics study of the closed form of the P2X$_4$ receptor. The fluctuations observed in the simulations were compared with the changes that occur in the transition from the closed to the open structure. In order to get further insight on the opening mechanism, the actual displacements were decomposed into inter-chain motions and intra-chain deformations. This analysis revealed that the iris like expansion of the transmembrane helices mainly results from inter-chain motions that already take place in the closed conformation. However, they cannot reach the amplitude required for the opening of the channel because they are impeded by interactions occurring around the ATP binding pocket. This suggests that the internal deformations of the chains, caused by the binding of ATP, would release these impediments allowing the aperture of the pore.