Methodology Summary

Here are a couple points on the process of this discovery- for those of you who are interested in methodology and lab protocols!

- The zebrafish α1 GlyR (NP_571477) was isolated for structural elucidation as it shares 92% sequence similarity with the human α1 GlyR and modified to resemble the human phenotype.

- GlyREM was then subcloned into a pGEM vector for transcription using Ambion, to be used for two-electrode voltage clamp electrophysiology (TEVC). TEVC is used to measure the ion currents through cell membranes.

- Crystalline structures of GlyREM were obtained using the hanging-drop vapour diffusion method with the data being collected using a Titan Krios cryo-electron microscope. Super resolution images were then determined using the Gatan K2 Summit direct electron detector.

And a little background about cryo-electron microscopy (cryo-EM)...

Cryo-EM is transmission electron microscopy at cryogenic temperatures. Contrary to X-ray crystallography, this allows for structures to be determined in their native environment. Recent advances in cryo-EM have resulted in structural elucidation at very high resolutions. In June 2015, a map of a complex between E. coli β-galactosidase and inhibitor phenylethyl-β-D-thiogalactopyranoside was resolved to 2.2 Å, the highest resolution to date.



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