論文：Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies
- クライオ電⼦顕微鏡を⽤いた単粒⼦解析法により、電位・カルシウムイオン依存性ATP透過性イオンチャネルCALHM1の構造を明らかにした。
- CALHM1はアルツハイマー型認知症のリスク因子であり、神経伝達因子の放出や味覚の感知に関与する。
- ヒト、魚、線虫のCALHM1の高分解能構造を決定し、このイオンチャネルの多量体化及び開閉機構を提唱した。
Abstract
Calcium homeostasis modulator (CALHM) family proteins are Ca2+-regulated adenosine triphosphate (ATP)–release channels involved in neural functions including neurotransmission in gustation. Here, we present the cryo–electron microscopy (EM) structures of killifish CALHM1, human CALHM2, and Caenorhabditis elegans 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.
分解能
2.66 ～ 3.6 Å
Citation
- Demura, T. Kusakizako, W. Shihoya, M. Hiraizumi, K. Nomura, H. Shimada, K. Yamashita, T. Nishizawa, A. Taruno and O. Nureki. Sci. Adv. Jul 17;6(29):eaba8105 (2020).
