Title
Stromal Interaction Molecule (STIM) 1 and STIM2 Calcium Sensing Regions Exhibit Distinct Unfolding and Oligomerization Kinetics
Author
Peter B. Stathopulos, Le Zheng, Mitsuhiko Ikura
Year
2008
Journal
The Journal of Biological Chemistry
Abstract
Stromal interaction molecules (STIM) 1 and STIM2 are regulators of store-operated calcium (Ca2+) entry as well as basal cytoplasmic Ca2+ levels in human cells. Despite a high sequence similarity (>65%) and analogous sequence-based domain architectures, STIM1 and STIM2 differentially influence these phenomena. Among all eukaryotes, the endoplasmic reticulum luminal portion of STIM proteins minimally encode EF-hand and sterile α-motif (SAM) domains (EF-SAM), which are responsible for sensing changes in Ca2+ levels and initiating oligomerization. STIM oligomerization is a key induction step in the activation of Ca2+-permeable channels on the plasma membrane. Here, we show that the kinetic half-time of conversion from a monomeric to a steady oligomeric state is >70× shorter for STIM1 EF-SAM than STIM2 under similar conditions. Urea-induced rates of unfolding for STIM1 EF-SAM are >3× quicker when compared with STIM2, coherent with partial unfolding-coupled aggregation. Additionally, we demonstrate that the isoform-specific N-terminal residues beyond EF-SAM can influence the stability of this region. We postulate that distinct oligomerization dynamics of STIM isoforms have evolved to adapt to differential roles in Ca2+homeostasis and signaling.
Full Article
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Kinetics, Thermal stability, Ligand binding, Biochemistry