Molecular Dynamic Simulations Reveal the Activation Mechanisms of Oxidation-Induced TRPV1.

ABSTRACT: Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, can be directly activated by oxidants through cysteine modification. However, the patterns of cysteine modification are unclear. Structural analysis showed that the free sulfhydryl groups of residue pairs C387 and C391 were potentially oxidized to form a disulfide bond, which is expected to be closely related to the redox sensing of TRPV1. To investigate if and how the redox states of C387 and C391 activate TRPV1, homology modeling and accelerated molecular dynamic simulations were performed. The simulation revealed the conformational transfer during the opening or closing of the channel. The formation of a disulfide bond between C387 and C391 leads to the motion of pre-S1, which further propagates conformati

SUBMITTER: Chu Y 

PROVIDER: S-EPMC10253787 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature