Anatrace社 Glyco-Diosgenin and Ion Channels: A Great Match!
The 2021 Nobel Prize in Physiology or Medicine awarded to Drs. Julius and Patapoutian “for their discoveries of receptors for temperature and touch” highlighted the recent successes in ion channel research. These important drug targets are present in the membranes of all cell types and are famously difficult (or even impossible) to crystallize. Add to that the ongoing ‘resolution revolution’ in cryo-EM and we have a winning case for this protein class!
Indeed, the PDB database has contained a consistently high number of ion channel structures over the years, with 738 in 2019 and 744 in 2020. Efforts to combat COVID-19 slowed down the research, reducing the count to 614 in 2021, but current trending makes us expect 2020’s record will be easily surpassed in 2022!
The Anatrace surfactant glyco-diosgenin (GDN), a drop-in substitute for the plant-derived digitonin, has been a helpful tool for stabilizing complex and fragile ion channels in this research. GDN is widely used for solubilization, purification, and stabilization of membrane proteins, and has significant advantages over digitonin: no batch-to-batch variability, none of the harmful toxic byproducts commonly found in digitonin, and a lower cost!
We are excited to share a list of recent, high-impact publications we’ve read that make great use of the GDN/cryo-EM combo in tackling ion channels:
1 Neuberger, A., Nadezhdin, K. D. & Sobolevsky, A. I. Structural mechanism of TRPV3 channel inhibition by the anesthetic dyclonine. Nat Commun 13, 2795 (2022).
2 Lam, A. K. M., Rutz, S. & Dutzler, R. Inhibition mechanism of the chloride channel TMEM16A by the pore blocker 1PBC. Nat Commun 13, 2798 (2022).
3 Ye, W. et al. Activation and closed-state inactivation mechanisms of the human voltage-gated KV4 channel complexes. Mol Cell (2022) doi:10.1016/j.molcel.2022.04.032.
4 Zhang, J. et al. N-type fast inactivation of a eukaryotic voltage-gated sodium channel. Nat Commun 13, 2713 (2022).
5 Kang, Y. & Chen, L. Structure and mechanism of NALCN-FAM155A-UNC79-UNC80 channel complex. Nat Commun 13, 2639 (2022).
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