Molecular dynamics simulations reveal the hidden EF-hand of EF-SAM as a possible key thermal sensor for STIM1 activation by temperature.

ABSTRACT: Intracellular calcium signaling is essential for many cellular processes, including store-operated Ca²⁺ entry (SOCE), which is initiated by stromal interaction molecule 1 (STIM1) detecting endoplasmic reticulum (ER) Ca²⁺ depletion. STIM1 is also activated by temperature independent of ER Ca²⁺ depletion. Here we provide evidence, from advanced molecular dynamics simulations, that EF-SAM may act as a true temperature sensor for STIM1, with the prompt and extended unfolding of the hidden EF-hand subdomain (hEF) even at slightly elevated temperatures, exposing a highly conserved hydrophobic Phe108. Our study also suggests an interplay between Ca²⁺ and temperature sensing, as both, the canonical EF-hand subdomain (cEF) and the hidden EF-hand subdomain

SUBMITTER: Neamtu A 

PROVIDER: S-EPMC10400917 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature