The Impact of Mutation L138F/L210F on the Orai Channel: A Molecular Dynamics Simulation Study.

ABSTRACT: The calcium release-activated calcium channel, composed of the Orai channel and the STIM protein, plays a crucial role in maintaining the Ca²⁺ concentration in cells. Previous studies showed that the L138F mutation in the human Orai1 creates a constitutively open channel independent of STIM, causing severe myopathy, but how the L138F mutation activates Orai1 is still unclear. Here, based on the crystal structure of Drosophila melanogaster Orai (dOrai), molecular dynamics simulations for the wild-type (WT) and the L210F (corresponding to L138F in the human Orai1) mutant were conducted to investigate their structural and dynamical properties. The results showed that the L210F dOrai mutant tends to have a more hydrated hydrophobic region (V174 to F171), as well as more dilat

SUBMITTER: Zhang X 

PROVIDER: S-EPMC8592927 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature