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Mechanistic insights into the Orai channel by molecular dynamics simulations.
Semin Cell Dev Biol. 2019 10; 94:50-58.SC

Abstract

Highly Ca2+ selective channels trigger a large variety of cellular signaling processes in both excitable and non-excitable cells. Among these channels, the Orai channel is unique in its activation mechanism and its structure. It mediates Ca2+ influx into the cytosol with an extremely small unitary conductance over longer time-scales, ranging from minutes up to several hours. Its activation is regulated by the Ca2+ content of the endoplasmic reticulum (ER). Depletion of luminal [Ca2+]ER is sensed by the STIM1 single transmembrane protein that directly binds and gates the Orai1 channel. Orai mediated Ca2+ influx increases cytosolic Ca2+ from 100 nM up to low micromolar range close to the pore and thereby forms Ca2+ microdomains. Hence, these features of the Orai channel can trigger long-term signaling processes without affecting the overall Ca2+ content of a single living cell. Here we focus on the architecture and dynamic conformational changes within the Orai channel. This review summarizes current achievements of molecular dynamics simulations in combination with live cell recordings to address gating and permeation of the Orai channel with molecular precision.

Authors+Show Affiliations

Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Nové Hrady CZ-373 33, Czech Republic. Electronic address: bonhenry@nh.cas.cz.Institute for Biophysics, Johannes Kepler University Linz, A-4040 Linz, Austria.Gottfried Schatz Research Center, Medical University of Graz, A-8010 Graz, Austria.Gottfried Schatz Research Center, Medical University of Graz, A-8010 Graz, Austria.Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Nové Hrady CZ-373 33, Czech Republic; College of Biomedical Sciences, Larkin University, Miami, FL 33169, United States.Gottfried Schatz Research Center, Medical University of Graz, A-8010 Graz, Austria. Electronic address: rainer.schindl@medunigraz.at.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

30639326

Citation

Bonhenry, Daniel, et al. "Mechanistic Insights Into the Orai Channel By Molecular Dynamics Simulations." Seminars in Cell & Developmental Biology, vol. 94, 2019, pp. 50-58.
Bonhenry D, Schober R, Schmidt T, et al. Mechanistic insights into the Orai channel by molecular dynamics simulations. Semin Cell Dev Biol. 2019;94:50-58.
Bonhenry, D., Schober, R., Schmidt, T., Waldherr, L., Ettrich, R. H., & Schindl, R. (2019). Mechanistic insights into the Orai channel by molecular dynamics simulations. Seminars in Cell & Developmental Biology, 94, 50-58. https://doi.org/10.1016/j.semcdb.2019.01.002
Bonhenry D, et al. Mechanistic Insights Into the Orai Channel By Molecular Dynamics Simulations. Semin Cell Dev Biol. 2019;94:50-58. PubMed PMID: 30639326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanistic insights into the Orai channel by molecular dynamics simulations. AU - Bonhenry,Daniel, AU - Schober,Romana, AU - Schmidt,Tony, AU - Waldherr,Linda, AU - Ettrich,Rüdiger H, AU - Schindl,Rainer, Y1 - 2019/01/15/ PY - 2018/09/11/received PY - 2018/12/12/revised PY - 2019/01/05/accepted PY - 2019/1/15/pubmed PY - 2020/6/4/medline PY - 2019/1/15/entrez KW - Calcium KW - Gating KW - MD-simulations KW - Molecular dynamics KW - Orai KW - Orai1 KW - Pore KW - STIM SP - 50 EP - 58 JF - Seminars in cell & developmental biology JO - Semin. Cell Dev. Biol. VL - 94 N2 - Highly Ca2+ selective channels trigger a large variety of cellular signaling processes in both excitable and non-excitable cells. Among these channels, the Orai channel is unique in its activation mechanism and its structure. It mediates Ca2+ influx into the cytosol with an extremely small unitary conductance over longer time-scales, ranging from minutes up to several hours. Its activation is regulated by the Ca2+ content of the endoplasmic reticulum (ER). Depletion of luminal [Ca2+]ER is sensed by the STIM1 single transmembrane protein that directly binds and gates the Orai1 channel. Orai mediated Ca2+ influx increases cytosolic Ca2+ from 100 nM up to low micromolar range close to the pore and thereby forms Ca2+ microdomains. Hence, these features of the Orai channel can trigger long-term signaling processes without affecting the overall Ca2+ content of a single living cell. Here we focus on the architecture and dynamic conformational changes within the Orai channel. This review summarizes current achievements of molecular dynamics simulations in combination with live cell recordings to address gating and permeation of the Orai channel with molecular precision. SN - 1096-3634 UR - https://www.unboundmedicine.com/medline/citation/30639326/Mechanistic_insights_into_the_Orai_channel_by_molecular_dynamics_simulations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1084-9521(18)30037-5 DB - PRIME DP - Unbound Medicine ER -