Open AccessMolecular anatomy of the early events in STIM1 activation; oligomerization or conformational change?
Author(s) -
Marek Korzeniowski,
Éva Wisniewski,
Barbara Baird,
David Holowka,
Tamás Balla
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.205583
Subject(s) - stim1 , endoplasmic reticulum , biophysics , conformational change , coiled coil , soar , orai1 , biology , intramolecular force , gating , calmodulin , microbiology and biotechnology , biochemistry , stereochemistry , chemistry , computer science , artificial intelligence , enzyme
Decreased luminal ER Ca2+ concentration triggers oligomerization and clustering of the ER Ca2+-sensor, STIM1 to promote its association with plasma membrane Orai1 Ca2+ channels leading to increased Ca2+ influx. A key step in STIM1 activation is the release of its SOAR domain from an intramolecular clamp formed with the STIM1 first coiled-coil (CC1) region. Using a truncated STIM1(1-343) molecule that captures or releases the isolated SOAR domain depending on luminal ER Ca2+ concentrations, we analyzed the early molecular events that control the intramolecular clamp formed between the CC1 and SOAR domains. We found that STIM1 forms constitutive dimers and its CC1 domain can bind SOAR of another STIM1 molecule in trans. Artificial oligomerization failed to liberate the SOAR domain, or activate STIM1 unless the luminal Ca2+ sensing domains were removed. We propose that the release of SOAR from its CC1 interaction is controlled by changes in the orientation of the two CC1 domains in STIM1 dimers. Ca2+ unbinding in the STIM1 luminal domains initiates the conformational change allowing SOAR domain liberation and clustering leading to Orai1 channel activation.