| Full text | |
| Author(s): Show less - |
Gudlur, Aparna
[1]
;
Zeraik, Ana Eliza
[2, 1]
;
Hirve, Nupura
[1]
;
Rajanikanth, V.
[3, 1]
;
Bobkov, Andrey A.
[4]
;
Ma, Guolin
[5]
;
Zheng, Sisi
[6]
;
Wang, Youjun
[6]
;
Zhou, Yubin
[5]
;
Komives, Elizabeth A.
[7]
;
Hogan, Patrick G.
[8, 1, 9]
Total Authors: 11
|
| Affiliation: | [1] La Jolla Inst Allergy & Immunol, Div Signalling & Gene Express, La Jolla, CA 92037 - USA
[2] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13563120 Sao Carlos, SP - Brazil
[3] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 - USA
[4] Sanford Burnham Prebys Med Discovery Inst, Prot Prod & Anal Facil, La Jolla, CA 92037 - USA
[5] Texas A&M Univ, Coll Med, Inst Biosci & Technol, Ctr Translat Canc Res, Houston, TX 77030 - USA
[6] Beijing Normal Univ, Coll Life Sci, Beijing Key Lab Gene Resource & Mol Dev, Beijing 100875 - Peoples R China
[7] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92037 - USA
[8] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 - USA
[9] Univ Calif San Diego, Program Immunol, La Jolla, CA 92037 - USA
Total Affiliations: 9
|
| Document type: | Journal article |
| Source: | NATURE COMMUNICATIONS; v. 9, OCT 31 2018. |
| Web of Science Citations: | 7 |
| Abstract | |
Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca2+ levels to maintain cellular Ca2+ balance and to support Ca2+ signalling. The prevailing view has been that STIM1 senses reduced ER Ca2+ through dissociation of bound Ca2+ from a single EF-hand site, which triggers a dramatic loss of secondary structure and dimerization of the STIM1 luminal domain. Here we find that the STIM1 luminal domain has 5-6 Ca2+- binding sites, that binding at these sites is energetically coupled to binding at the EF-hand site, and that Ca2+ dissociation controls a switch to a second structured conformation of the luminal domain rather than protein unfolding. Importantly, the other luminal-domain Ca2+- binding sites interact with the EF-hand site to control physiological activation of STIM1 in cells. These findings fundamentally revise our understanding of physiological Ca2+ sensing by STIM1, and highlight molecular mechanisms that govern the Ca2+ threshold for activation and the steep Ca2+ concentration dependence. (AU) | |
| FAPESP's process: | 16/12505-8 - Characterization of the calcium release-activated (CRAC) channel in the human pathogen Schistosoma mansoni through the study of its components STIM and ORAI proteins |
| Grantee: | Ana Eliza Zeraik |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |