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K⁺ channels can convert between conductive and non-conductive forms through mechanisms that range from flicker transitions (which occur in microseconds) to C-type inactivation (which occurs on millisecond to second timescales). Here, the crystal structures are presented of the potassium channel KcsA in an open-inactivated conformation and 'trapped' in several partially open conformations. The structures indicate a molecular basis for C-type inactivation in K⁺ channels.

CorA is the major magnesium influx pathway in bacteria, but the mechanism for the uptake of magnesium by this system is not clear. Here, Dalmas et al.show that CorA is regulated by cytoplasmic magnesium levels, and determine the conformational changes required for the regulation by a negative feedback loop.

K⁺ channels can convert between conductive and non-conductive forms through mechanisms that range from flicker transitions (which occur in microseconds) to C-type inactivation (which occurs on millisecond to second timescales). Here, the mechanisms are revealed through which movements of the inner gate of the K⁺ channel KcsA trigger conformational changes at the selectivity filter, leading to the non-conductive C-type inactivated state.

Voltage-gated potassium channels control excitability, but their non-conductive structure remained elusive. Here, authors reveal the Shaker channel’s closed-pore structure, showing distinct “roll-and-turn” helix movements that redefine activation gating in the Kv1 family.

HERG channel inactivation is critical for normal heart rhythm. Authors determine structures of open and non-conducting states of HERG and identify a key role for S620 on the pore helix in coordinating transitions between open and inactivated states.

The allosteric communication between the pore domain, voltage sensors, and Ca2+ binding sites in BK channels underlies its physiological role. Here, cryo-EM structures provide a plausible path where voltage and Ca2+ binding define the conformation of the pore domain.

Mammalian prestin underlies cellular electromotility by sensing the voltage through a dynamic senor and converting it to an in-plane area expansion.

Mechanosensitive channels release tension in cell membranes by opening 'pressure relief' pores. The structure of a partially open channel suggests a gating mechanism and delivers an unexpected architectural twist.

A series of long molecular dynamics simulations shows that the K⁺ channel is sterically locked in the inactive conformation by buried water molecules bound behind the selectivity filter; a kinetic model deduced from the simulations shows how releasing the buried waters can elongate the timescale of the recovery period, and this hypothesis is confirmed using ‘wet’ biophysical experiments.

Recent structural and functional analyses of MthK, a prokaryotic Ca²⁺-activated K⁺ channel, suggest that the interplay between cytoplasmic Ca²⁺ and H⁺ concentrations determines the oligomeric stability of its associated RCK domain and thus controls activation gating. However, the discovery of a ligand-dependent desensitization process suggests that gating in these channels might be more complicated than originally envisioned.

Voltage sensor domains (VSDs) transducer changes in the electrical field across cell membranes into conformational changes that alter the activation state of an effector domain. Structural and biophysical data on the VSD from Ci-VSP reveal the first view of this domain in the resting state, providing new insight into voltage-dependent structural transitions.

The voltage-sensing domain (VSD) of voltage-gated ion channels transitions from a resting to an activated conformation upon membrane polarization. EPR spectroscopy analysis has now determined the position of the KvAP VSD in a resting conformation, revealing a new ‘tilt-shift’ model for transitioning between resting and activated states.

The cryo-electron microscopy structure of the hyperpolarization-activated K⁺ channel KAT1 points to a direct-coupling mechanism between S4 movement and the reorientation of the C-linker.

The human voltage-gated proton channel (hHv1) maintains intracellular pH and membrane potential in sperm and neutrophils. Here, the authors show that albumin activates hHv1, by binding to the channel voltage sensor domains to enhance open probability and increases proton current, and that activation is required to trigger sperm to allow oocyte fertilization and to sustain production and release of immune inflammatory mediators during the neutrophil respiratory burst.

The activation of bacterial mechanosensitive channels is still not fully understood. Here, Bavi et al. show that the N-terminal helix of MscL dynamically couples membrane tension to channel gating, suggesting a conserved mechanism underlying the mechanosensitivity of ion channels of higher organisms.

The K+ channels can display three distinct gating modes. The molecular basis for two of these modes (low open probability and flickery) are now examined by a combination of single-channel recording, crystallography and modeling of mutants in Glu71, revealing that changes in ion and water occupancy in and around the selectivity filter determine modal gating.

Prokaryotic mechanosensitive channels function as molecular switches that transduce bilayer deformations into protein motion. These structural rearrangements generate large non-selective pores that result in fast solute and solvent exchange and function as a prokaryotic 'last line of defence' to sudden osmotic challenges.