Exploration of inositol 1,4,5-trisphosphate (IP₃) regulated dynamics of N-terminal domain of IP₃ receptor reveals early phase molecular events during receptor activation.

ABSTRACT: Inositol 1, 4, 5-trisphosphate (IP₃) binding at the N-terminus (NT) of IP₃ receptor (IP₃R) allosterically triggers the opening of a Ca²⁺-conducting pore located ~100 Å away from the IP₃-binding core (IBC). However, the precise mechanism of IP₃ binding and correlated domain dynamics in the NT that are central to the IP₃R activation, remains unknown. Our all-atom molecular dynamics (MD) simulations recapitulate the characteristic twist motion of the suppressor domain (SD) and reveal correlated 'clam closure' dynamics of IBC with IP₃-binding, complementing existing suggestions on IP₃R activation mechanism. Our study further reveals the existence of inter-domain dynamic correlation in the NT and

SUBMITTER: Chandran A 

PROVIDER: S-EPMC6385359 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature