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Issues

ISSN 0022-1295
EISSN 1540-7748
In this Issue

Research News

New method predicts the molecular basis of membrane proteins’ voltage sensitivity.

Essay

JGP 100th Anniversary

Cheng recalls the multidisciplinary influence of his trans-Pacific training.

Commentary

Yeung and Prakriya highlight new research showing that STIM1 must bind to all six Orai1 subunits to effectively activate the channel.

Delemotte appraises new computational work revealing that the intracellular activation gate must open for C-type inactivation to occur in K+ channels.

Viewpoint

Burger et al. summarize our mechanistic understanding of allostery in the prototypical GPCR, the muscarinic acetylcholine receptor.

Article

The quantitative relation between STIM1 binding to Orai1 and store-operated CRAC channel activation is not well understood. Yen and Lewis find that STIM1 must bind to all six Orai1 subunits to effectively open the channel and generate the high ion selectivity and low conductance seen in native cells.

Neuronal plasticity in adulthood is important for adaptation to different environments. Frolov et al. show that rearing mature Periplaneta americana in prolonged light or dark leads to distinct changes in photoreceptor responses, suggesting remodeling of the light-sensitive membrane.

The origin of ion selectivity in epithelial Na+ channels and the closely related acid-sensing ion channels is uncertain. Yang and Palmer show that the site of ion selectivity in epithelial Na+ channels is more extracellular than that proposed for acid-sensing ion channels.

C-type inactivation in K+ channels is thought to be a result of constriction of the selectivity filter. By using MD simulations, Li et al. show that rapid constriction occurs within 1–2 s when the intracellular activation gate is fully open, but not when the gate is closed or partially open.

Retigabine is a widely studied potassium channel activator that is thought to interact with a conserved Trp side chain in the pore domain of Kv7 subunits. Yau et al. demonstrate that drug sensitivity in just one of the four subunits is sufficient for a near-maximal response to retigabine.

Kv7 potassium channels are strongly activated by a variety of small molecules with diverse mechanisms of action. Wang et al. investigate a compound that targets the voltage-sensing domain, ICA-069673, and demonstrate that four drug-sensitive subunits are required for maximal effect.

The identification of voltage-sensing elements in membrane proteins is challenging due to the diversity of voltage-sensing mechanisms. Kasimova et al. present a computational approach to predict the elements involved in voltage sensing, which they validate using voltage-gated ion channels.

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