Molecular basis of allosteric Orai1 channel activation by STIM1.

Molecular basis of allosteric Orai1 channel activation by STIM1.
J Physiol. 2019 Apr 05;:
Authors: Yeung PS, Yamashita M, Prakriya M
Abstract
Store-operated Ca2+ entry through Orai1 channels is a primary mechanism for Ca2+ entry in many cells and mediates a variety of cellular effector functions ranging from gene transcription to exocytosis. Orai1 channels are amongst the most Ca2+ selective channels known and are activated by direct physical interactions with the endoplasmic reticulum (ER) Ca2+ sensor, STIM1, in response to store depletion triggered by stimulation of a variety of cell surface G-protein coupled and tyrosine kinase receptors. Work in the last decade has revealed that the Orai1 gating process is highly cooperative and strongly allosteric, likely driven by a wave of inter-dependent conformational changes throughout the protein originating in the peripheral C-terminal ligand binding site and culminating in pore opening. In this review, we survey the structural and molecular features in Orai1 that contribute to channel gating and consider how they give rise to the unique biophysical fingerprint of Orai1 currents.
PMID: 30950063 [PubMed - as supplied by publisher]

Source: The Journal of Physiology - April 4, 2019 Category: Physiology Authors: Yeung PS, Yamashita M, Prakriya M Tags: J Physiol Source Type: research