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Gene Synthesis> | The full-length human CALHM1, CALHM2 and CALHM3 genes (http:// www.uniprot.org; UniProtKB numbers: Q8IU99, Q9HA72 and Q86XJ0, respectively) were synthesized by Genscript and subcloned into a pEG BacMam vector comprising an N- or C-terminal thrombin cleavage site, GFP and His8 tag30 | Get A Quote |
Calcium homeostasis modulators (CALHMs) are voltage-gated, Ca2+-inhibited nonselective ion channels that act as major ATP release channels, and have important roles in gustatory signalling and neuronal toxicity1-3. Dysfunction of CALHMs has previously been linked to neurological disorders1. Here we present cryo-electron microscopy structures of the human CALHM2 channel in the Ca2+-free active or open state and in the ruthenium red (RUR)-bound inhibited state, at resolutions up to 2.7 Å. Our work shows that purified CALHM2 channels form both gap junctions and undecameric hemichannels. The protomer shows a mirrored arrangement of the transmembrane domains (helices S1-S4) relative to other channels with a simila... More