Structural insights into glucose-6-phosphate recognition and hydrolysis by human G6PC1.

The glucose-6-phosphatase (G6Pase) is an integral membrane protein that catalyzes the hydrolysis of glucose-6-phosphate (G6P) in the endoplasmic reticulum lumen and plays a vital role in glucose homeostasis. Dysregulation or genetic mutations of G6Pase are associated with diabetes and glycogen storage disease 1a (GSD-1a). Studies have characterized the biophysical and biochemical properties of G6Pase; however, the structure and substrate recognition mechanism of G6Pase remain unclear.

Structural mechanism of voltage-gated sodium channel slow inactivation.

Voltage-gated sodium (Na) channels mediate a plethora of electrical activities. Na channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of Na channels that regulates cellular excitability by controlling the channel availability.

Structural Advances in Voltage-Gated Sodium Channels.

Voltage-gated sodium (Na) channels are responsible for the rapid rising-phase of action potentials in excitable cells. Over 1,000 mutations in Na channels are associated with human diseases including epilepsy, periodic paralysis, arrhythmias and pain disorders. Natural toxins and clinically-used small-molecule drugs bind to Na channels and modulate their functions.

N-type fast inactivation of a eukaryotic voltage-gated sodium channel.

Voltage-gated sodium (Na) channels initiate action potentials. Fast inactivation of Na channels, mediated by an Ile-Phe-Met motif, is crucial for preventing hyperexcitability and regulating firing frequency. Here we present cryo-electron microscopy structure of NaEh from the coccolithophore Emiliania huxleyi, which reveals an unexpected molecular gating mechanism for Na channel fast inactivation independent of the Ile-Phe-Met motif.