Mechanistic insights into the Orai channel by molecular dynamics simulations

0519579 - MBÚ 2020 RIV GB eng J - Článek v odborném periodiku
Bonhenry, Daniel - Schober, R. - Schmidt, T. - Waldherr, L. - Ettrich, Rüdiger - Schindel, R.
Mechanistic insights into the Orai channel by molecular dynamics simulations.
Seminars in Cell & Developmental Biology. Roč. 94, October 2019 SI (2019), s. 50-58. ISSN 1084-9521. E-ISSN 1096-3634
Grant CEP: GA ČR(CZ) GA13-21053S; GA MŠMT(CZ) LM2015055; GA MŠMT(CZ) LM2015055; GA MŠMT(CZ) LTC17069
GRANT EU: European Commission(CZ) ATCZ14 EFRR Project Interreg Austria-Czech Republic; European Commission(CZ) BM 1406
Výzkumná infrastruktura: C4SYS - 90055
Institucionální podpora: RVO:61388971
Klíčová slova: Molecular dynamics * MD-simulations * Orai
Obor OECD: Biophysics
Impakt faktor: 6.691, rok: 2019
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S1084952118300375?via%3Dihub

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 Orail 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.
Trvalý link: http://hdl.handle.net/11104/0304574