Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies
K. Demura, Tsukasa Kusakizako, Wataru Shihoya, Masahiro Hiraizumi, Kengo Nomura, H. Shimada, Keitaro Yamashita, Tomohiro Nishizawa, Akiyuki Taruno, Osamu Nureki
Abstract
CLHM-1 at resolutions of 2.66, 3.4, and 3.6 Å, 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 nonamer structures show the different oligomeric stoichiometries among CALHM homologs. We further report the cryo-EM structures of the chimeric construct, revealing that the intersubunit interactions at the transmembrane domain (TMD) and the TMD-intracellular domain linker define the oligomeric stoichiometry. These findings advance our understanding of the ATP conduction and oligomerization mechanisms of CALHM channels.