Academic Journal
Conformational dynamics of auto-inhibition in the ER calcium sensor STIM1
| العنوان: | Conformational dynamics of auto-inhibition in the ER calcium sensor STIM1 |
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| المؤلفون: | van Dorp, Stijn, Qiu, Ruoyi, Choi, Ucheor B, Wu, Minnie M, Yen, Michelle, Kirmiz, Michael, Brunger, Axel T, Lewis, Richard S |
| المساهمون: | National Institutes of Health, Mathers Foundation, Stanford University, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, American Heart Association |
| المصدر: | eLife ; volume 10 ; ISSN 2050-084X |
| بيانات النشر: | eLife Sciences Publications, Ltd |
| سنة النشر: | 2021 |
| المجموعة: | eLife (E-Journal - via CrossRef) |
| الوصف: | The dimeric ER Ca 2+ sensor STIM1 controls store-operated Ca 2+ entry (SOCE) through the regulated binding of its CRAC activation domain (CAD) to Orai channels in the plasma membrane. In resting cells, the STIM1 CC1 domain interacts with CAD to suppress SOCE, but the structural basis of this interaction is unclear. Using single-molecule Förster resonance energy transfer (smFRET) and protein crosslinking approaches, we show that CC1 interacts dynamically with CAD in a domain-swapped configuration with an orientation predicted to sequester its Orai-binding region adjacent to the ER membrane. Following ER Ca 2+ depletion and release from CAD, cysteine crosslinking indicates that the two CC1 domains become closely paired along their entire length in the active Orai-bound state. These findings provide a structural basis for the dual roles of CC1: sequestering CAD to suppress SOCE in resting cells and propelling it toward the plasma membrane to activate Orai and SOCE after store depletion. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.7554/elife.66194 |
| الاتاحة: | http://dx.doi.org/10.7554/elife.66194 https://cdn.elifesciences.org/articles/66194/elife-66194-v2.pdf https://cdn.elifesciences.org/articles/66194/elife-66194-v2.xml https://elifesciences.org/articles/66194 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.BDE8B6B5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.7554/elife.66194 |
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