We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Initial activation of STIM1, the regulator of store-operated calcium entry.
- Authors
Zhou, Yubin; Srinivasan, Prasanna; Razavi, Shiva; Seymour, Sam; Meraner, Paul; Gudlur, Aparna; Stathopulos, Peter B; Ikura, Mitsuhiko; Rao, Anjana; Hogan, Patrick G
- Abstract
Physiological Ca2+ signaling in T lymphocytes and other cells depends on the STIM-ORAI pathway of store-operated Ca2+ entry. STIM1 and STIM2 are Ca2+ sensors in the endoplasmic reticulum (ER) membrane, with ER-luminal domains that monitor cellular Ca2+ stores and cytoplasmic domains that gate ORAI channels in the plasma membrane. The STIM ER-luminal domain dimerizes or oligomerizes upon dissociation of Ca2+, but the mechanism transmitting activation to the STIM cytoplasmic domain was previously undefined. Using Tb3+-acceptor energy transfer, we show that dimerization of STIM1 ER-luminal domains causes an extensive conformational change in mouse STIM1 cytoplasmic domains. The conformational change, triggered by apposition of the predicted coiled-coil 1 (CC1) regions, releases the ORAI-activating domains from their interaction with the CC1 regions and allows physical extension of the STIM1 cytoplasmic domain across the gap between ER and plasma membrane and communication with ORAI channels.
- Subjects
T cells; STROMAL cells; ENDOPLASMIC reticulum; DIMERIZATION; DISSOCIATION (Chemistry); CALCIUM channels; CELL membranes; PHYSIOLOGY
- Publication
Nature Structural & Molecular Biology, 2013, Vol 20, Issue 8, p973
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2625