Communication between N terminus and loop2 tunes Orai activation

0489833 - MBÚ 2019 RIV US eng J - Článek v odborném periodiku
Fahrner, M. - Pandey, Saurabh Kumar - Muik, M. - Traxler, L. - Butorac, C. - Stadlbauer, M. - Zayats, Vasilina - Křížová, A. - Plenk, P. - Frischauf, I. - Schindl, R. - Gruber, H.J. - Hinterdorfer, P. - Ettrich, Rüdiger - Romanin, C. - Derler, I.
Communication between N terminus and loop2 tunes Orai activation.
Journal of Biological Chemistry. Roč. 293, č. 4 (2018), s. 1271-1285. ISSN 0021-9258. E-ISSN 1083-351X
Grant CEP: GA MŠMT(CZ) LTC17069
GRANT EU: European Commission(CZ) COST Action BM1406
Institucionální podpora: RVO:61388971
Klíčová slova: atomic force microscopy (AFM) * calcium release-activated calcium channel protein 1 (ORAI1) * electrophysiology
Obor OECD: Microbiology
Impakt faktor: 4.106, rok: 2018

The CRAC channel gating involves the binding of STIM1 C-terminus to cytosolic N- and C-termini of Orai. The C-termini of Orai is the main binding partner however N-termini also have been found necessary for Orai channel function. Despite a highly conserved ETON region Orai1 and Orai3 differ in length of the ETON region. Our aim here was to study the reasons for different behavior of these two isoforms and to find the differences in structural requirement for gating and function. While there is no interaction between the N-terminus and loop2 in Orai3, we predict that interactions between loop2 and Orai1 N-terminus results into masking the STIM1 coupling sites which are located either at N-terminus or loop2 or both, thus loop2 either directly or allosterically affects the STIM1-Orai coupling in an isoform specific manner. Thus along with the requirement of conserved ETON region a fine tuning between N-termini and loop2 conformations has an essential role in maintaining permissive conformation of channel and store-operated function of Orai channel.


Trvalý link: http://hdl.handle.net/11104/0284168