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The STIM-Orai coupling interface and gating of the Orai1 channel.
Cell Calcium. 2017 05; 63:8-13.CC

Abstract

In virtually all cells, store-operated Ca2+ entry signals are vital in controlling a spectrum of functions. The signals are mediated by STIM proteins in the ER and Orai channels in the PM which undergo a dynamic coupling process within discrete ER-PM junctional regions. This coupling is initiated by depletion of ER stored Ca2+ triggering STIM proteins to undergo an intricate activation process. Thereafter, STIM proteins become trapped in the ER-PM junctions where they tether and gate PM Orai Ca2+ channels. STIM1 exists as a dimer, with a single STIM-Orai activating region (SOAR) buried in the resting protein that becomes exposed upon activation. An exposed region on SOAR including the Phe-394 residue forms a critical Orai1 interacting site. Using dimeric SOAR concatemers, we reveal only one of the two sites in the SOAR dimer is needed for Orai1 activation. This unimolecular interaction of SOAR with Orai1 suggests STIM1 can cross-link Orai channels with important significance for Ca2+ signaling. A critical "nexus" region in Orai1 close to the STIM1-binding site can be mutated to constitutively activate the channel mimicking the gating action of STIM1. This indicates STIM1 remotely controls Orai1 channel gating through an allosteric switch triggered by STIM1 binding only to the exposed C-terminal tail of the Orai1 channel.

Authors+Show Affiliations

Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. Electronic address: zhouyd@psu.edu.Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.Beijing Key Laboratory of Gene Resources and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, PR China.Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. Electronic address: dongill@psu.edu.

Pub Type(s)

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

Language

eng

PubMed ID

28087079

Citation

Zhou, Yandong, et al. "The STIM-Orai Coupling Interface and Gating of the Orai1 Channel." Cell Calcium, vol. 63, 2017, pp. 8-13.
Zhou Y, Cai X, Nwokonko RM, et al. The STIM-Orai coupling interface and gating of the Orai1 channel. Cell Calcium. 2017;63:8-13.
Zhou, Y., Cai, X., Nwokonko, R. M., Loktionova, N. A., Wang, Y., & Gill, D. L. (2017). The STIM-Orai coupling interface and gating of the Orai1 channel. Cell Calcium, 63, 8-13. https://doi.org/10.1016/j.ceca.2017.01.001
Zhou Y, et al. The STIM-Orai Coupling Interface and Gating of the Orai1 Channel. Cell Calcium. 2017;63:8-13. PubMed PMID: 28087079.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The STIM-Orai coupling interface and gating of the Orai1 channel. AU - Zhou,Yandong, AU - Cai,Xiangyu, AU - Nwokonko,Robert M, AU - Loktionova,Natalia A, AU - Wang,Youjun, AU - Gill,Donald L, Y1 - 2017/01/08/ PY - 2016/12/16/received PY - 2017/01/05/revised PY - 2017/01/05/accepted PY - 2017/1/15/pubmed PY - 2018/3/27/medline PY - 2017/1/15/entrez KW - Calcium channels KW - Calcium signals KW - Orai1 KW - STIM1 KW - Store-operated SP - 8 EP - 13 JF - Cell calcium JO - Cell Calcium VL - 63 N2 - In virtually all cells, store-operated Ca2+ entry signals are vital in controlling a spectrum of functions. The signals are mediated by STIM proteins in the ER and Orai channels in the PM which undergo a dynamic coupling process within discrete ER-PM junctional regions. This coupling is initiated by depletion of ER stored Ca2+ triggering STIM proteins to undergo an intricate activation process. Thereafter, STIM proteins become trapped in the ER-PM junctions where they tether and gate PM Orai Ca2+ channels. STIM1 exists as a dimer, with a single STIM-Orai activating region (SOAR) buried in the resting protein that becomes exposed upon activation. An exposed region on SOAR including the Phe-394 residue forms a critical Orai1 interacting site. Using dimeric SOAR concatemers, we reveal only one of the two sites in the SOAR dimer is needed for Orai1 activation. This unimolecular interaction of SOAR with Orai1 suggests STIM1 can cross-link Orai channels with important significance for Ca2+ signaling. A critical "nexus" region in Orai1 close to the STIM1-binding site can be mutated to constitutively activate the channel mimicking the gating action of STIM1. This indicates STIM1 remotely controls Orai1 channel gating through an allosteric switch triggered by STIM1 binding only to the exposed C-terminal tail of the Orai1 channel. SN - 1532-1991 UR - https://www.unboundmedicine.com/medline/citation/28087079/The_STIM_Orai_coupling_interface_and_gating_of_the_Orai1_channel_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4160(16)30224-X DB - PRIME DP - Unbound Medicine ER -