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Initial activation of STIM1, the regulator of store-operated calcium entry.


ABSTRACT: Physiological Ca(2+) signaling in T lymphocytes and other cells depends on the STIM-ORAI pathway of store-operated Ca(2+) entry. STIM1 and STIM2 are Ca(2+) sensors in the endoplasmic reticulum (ER) membrane, with ER-luminal domains that monitor cellular Ca(2+) stores and cytoplasmic domains that gate ORAI channels in the plasma membrane. The STIM ER-luminal domain dimerizes or oligomerizes upon dissociation of Ca(2+), but the mechanism transmitting activation to the STIM cytoplasmic domain was previously undefined. Using Tb(3+)-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.

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC3784406 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Initial activation of STIM1, the regulator of store-operated calcium entry.

Zhou Yubin Y   Srinivasan Prasanna P   Razavi Shiva S   Seymour Sam S   Meraner Paul P   Gudlur Aparna A   Stathopulos Peter B PB   Ikura Mitsuhiko M   Rao Anjana A   Hogan Patrick G PG  

Nature structural & molecular biology 20130714 8


Physiological Ca(2+) signaling in T lymphocytes and other cells depends on the STIM-ORAI pathway of store-operated Ca(2+) entry. STIM1 and STIM2 are Ca(2+) sensors in the endoplasmic reticulum (ER) membrane, with ER-luminal domains that monitor cellular Ca(2+) stores and cytoplasmic domains that gate ORAI channels in the plasma membrane. The STIM ER-luminal domain dimerizes or oligomerizes upon dissociation of Ca(2+), but the mechanism transmitting activation to the STIM cytoplasmic domain was p  ...[more]

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