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bioRxiv · 10.1101/2020.01.31.928093

Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies

Demura, K.·Kusakizako, T.·Shihoya, W.·Hiraizumi, M.·Nomura, K.·Shimada, H.·Yamashita, K.·Nishizawa, T.·Taruno, A.·Nureki, O.
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Abstract

Calcium homeostasis modulator (CALHM) family proteins are Ca2+-regulated ATP-release channels involved in neural functions including neurotransmission in gustation. Here we present the cryo-EM structures of killifish CALHM1, human CALHM2, and C. elegans CLHM-1 at resolutions of 2.66, 3.51, and 3.60 [A], respectively. The CALHM1 octamer structure reveals that the N-terminal helix forms the constriction site at the channel pore in the open state, and modulates the ATP conductance. The CALHM2 undecamer and CLHM-1 nonomer structures show the different oligomeric stoichiometries among CALHM homologs. We further report the cryo-EM structures of the chimeric construct, revealing that the inter-subunit interactions at the transmembrane domain define the oligomeric stoichiometry. These findings advance our understanding of the ATP conduction and oligomerization mechanisms of CALHM channels. One Sentence SummaryCryo-EM structures reveal the ATP conduction and oligomeric assembly mechanisms of CALHM channels.

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Demura, K., Kusakizako, T., Shihoya, W., Hiraizumi, M., Nomura, K., Shimada, H., Yamashita, K., Nishizawa, T., Taruno, A., Nureki, O.. 2020-01-31. Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies. https://doi.org/10.1101/2020.01.31.928093

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