STIM1 transmembrane helix dimerization captured by AI-guided transition path sampling.

ABSTRACT: Stromal interaction molecule 1 (STIM1) is a Ca²⁺-sensing protein in the endoplasmic reticulum (ER) membrane. The depletion of ER Ca²⁺ stores induces a large conformational transition of the cytosolic STIM1 C-terminus, initiated by the dimerization of the transmembrane (TM) domain. We use the AI-guided transition path sampling algorithm aimmd to extensively sample the dimerization of STIM1-TM helices in an ER-mimicking lipid bilayer. In nearly 0.5 ms of all-atom molecular dynamics simulations without bias potentials, we harvest over 170 transition paths, each about 1.2 μs long on average. We find that STIM1 dimerizes into three distinct and coexisting configurations, which reconciles conflicting results from earlier crosslinking studies. The dominant X-shaped bound sta

SUBMITTER: Horvath F 

PROVIDER: S-EPMC12415195 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature