Gating mechanism of a P2X4 receptor developed from normal mode analysis and molecular dynamics simulations.

ABSTRACT: P2X receptors are trimeric ATP-gated cation channels participating in diverse physiological processes. How ATP binding triggers channel opening remains unclear. Here the gating mechanism of a P2X receptor was studied by normal mode analysis and molecular dynamics (MD) simulations. Based on the resting-state crystal structure, a normal mode involving coupled motions of three β-strands (β1, β13, and β14) at the trimeric interface of the ligand-binding ectodomain and the pore-lining helix (TM2) in the transmembrane domain (TMD) was identified. The resulting widening of the fenestrations above the TMD and opening of the transmembrane pore produce known signatures of channel activation. In MD simulations, ATP was initially placed in the putative binding pocket (defined by four charged residues

SUBMITTER: Du J 

PROVIDER: S-EPMC3306669 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature