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Coiled-Coil Formation Conveys a STIM1 Signal from ER Lumen to Cytoplasm.
Cell Rep. 2018 01 02; 22(1):72-83.CR

Abstract

STIM1 and STIM2 are endoplasmic reticulum (ER) membrane proteins that sense decreases in ER-luminal free Ca2+ and, through a conformational change in the STIM cytoplasmic domain, control gating of the plasma membrane Ca2+ channel ORAI1. To determine how STIM1 conveys a signal from the ER lumen to the cytoplasm, we studied the Ca2+-dependent conformational change of engineered STIM1 proteins in isolated ER membranes and, in parallel, physiological activation of these proteins in cells. We find that conserved "sentinel" features of the CC1 region help to prevent activation while Ca2+ is bound to STIM ER-luminal domains. Reduced ER-luminal Ca2+ drives a concerted conformational change, in which STIM luminal domains rearrange and the STIM transmembrane helices and initial parts of the CC1 regions pair in an extended coiled coil. This intradimer rearrangement overcomes the relatively weak CC1-SOAR/CAD interactions that hold STIM in an inactive conformation, releasing the SOAR/CAD domain to activate ORAI channels.

Authors+Show Affiliations

Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Program in Immunology, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: phogan@lji.org.Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29298434

Citation

Hirve, Nupura, et al. "Coiled-Coil Formation Conveys a STIM1 Signal From ER Lumen to Cytoplasm." Cell Reports, vol. 22, no. 1, 2018, pp. 72-83.
Hirve N, Rajanikanth V, Hogan PG, et al. Coiled-Coil Formation Conveys a STIM1 Signal from ER Lumen to Cytoplasm. Cell Rep. 2018;22(1):72-83.
Hirve, N., Rajanikanth, V., Hogan, P. G., & Gudlur, A. (2018). Coiled-Coil Formation Conveys a STIM1 Signal from ER Lumen to Cytoplasm. Cell Reports, 22(1), 72-83. https://doi.org/10.1016/j.celrep.2017.12.030
Hirve N, et al. Coiled-Coil Formation Conveys a STIM1 Signal From ER Lumen to Cytoplasm. Cell Rep. 2018 01 2;22(1):72-83. PubMed PMID: 29298434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coiled-Coil Formation Conveys a STIM1 Signal from ER Lumen to Cytoplasm. AU - Hirve,Nupura, AU - Rajanikanth,Vangipurapu, AU - Hogan,Patrick G, AU - Gudlur,Aparna, PY - 2017/09/12/received PY - 2017/11/07/revised PY - 2017/12/10/accepted PY - 2018/1/4/entrez PY - 2018/1/4/pubmed PY - 2019/3/28/medline KW - ER-plasma membrane junction KW - STIM1 KW - STIM2 KW - calcium imaging KW - coiled coil KW - conformational change KW - disulfide crosslinking KW - evolution KW - store-operated calcium entry KW - transmembrane SP - 72 EP - 83 JF - Cell reports JO - Cell Rep VL - 22 IS - 1 N2 - STIM1 and STIM2 are endoplasmic reticulum (ER) membrane proteins that sense decreases in ER-luminal free Ca2+ and, through a conformational change in the STIM cytoplasmic domain, control gating of the plasma membrane Ca2+ channel ORAI1. To determine how STIM1 conveys a signal from the ER lumen to the cytoplasm, we studied the Ca2+-dependent conformational change of engineered STIM1 proteins in isolated ER membranes and, in parallel, physiological activation of these proteins in cells. We find that conserved "sentinel" features of the CC1 region help to prevent activation while Ca2+ is bound to STIM ER-luminal domains. Reduced ER-luminal Ca2+ drives a concerted conformational change, in which STIM luminal domains rearrange and the STIM transmembrane helices and initial parts of the CC1 regions pair in an extended coiled coil. This intradimer rearrangement overcomes the relatively weak CC1-SOAR/CAD interactions that hold STIM in an inactive conformation, releasing the SOAR/CAD domain to activate ORAI channels. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/29298434/Coiled_Coil_Formation_Conveys_a_STIM1_Signal_from_ER_Lumen_to_Cytoplasm_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(17)31839-9 DB - PRIME DP - Unbound Medicine ER -