Toward a Model for Activation of Orai Channel.
iScience
; 16: 356-367, 2019 Jun 28.
Article
en En
| MEDLINE
| ID: mdl-31207498
ABSTRACT
Store-operated calcium release-activated calcium (CRAC) channels mediate a variety of cellular signaling functions. The CRAC channel pore-forming protein, Orai1, is a hexamer arranged with 3-fold symmetry. Despite its importance in moving Ca2+ ions into cells, a detailed mechanistic understanding of Orai1 activation is lacking. Herein, a working model is proposed for the putative open state of Orai from Drosophila melanogaster (dOrai), which involves a "twist-to-open" gating mechanism. The proposed model is supported by energetic, structural, and experimental evidence. Fluorescent imaging demonstrates that each subunit on the intracellular side of the pore is inherently strongly cross-linked, which is important for coupling to STIM1, the pore activator, and graded activation of the Orai1 channel. The proposed model thus paves the way for understanding key aspects of calcium signaling at a molecular level.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
IScience
Año:
2019
Tipo del documento:
Article