National Natural Science Foundation of China (NSFC)
31870736
中国
National Natural Science Foundation of China (NSFC)
91954119
中国
National Natural Science Foundation of China (NSFC)
31870834
中国
National Natural Science Foundation of China (NSFC)
31570750
中国
引用
ジャーナル: Sci Adv / 年: 2020 タイトル: Cryo-EM structure of the calcium homeostasis modulator 1 channel. 著者: Yue Ren / Tianlei Wen / Zhiqin Xi / Shunjin Li / Jing Lu / Xing Zhang / Xue Yang / Yuequan Shen / 要旨: Calcium homeostasis modulator 1 (CALHM1) is a voltage-gated ATP release channel that plays an important role in neural gustatory signaling and the pathogenesis of Alzheimer's disease. Here, we ...Calcium homeostasis modulator 1 (CALHM1) is a voltage-gated ATP release channel that plays an important role in neural gustatory signaling and the pathogenesis of Alzheimer's disease. Here, we present a cryo-electron microscopy structure of full-length Ca-free CALHM1 from Danio rerio at an overall resolution of 3.1 Å. Our structure reveals an octameric architecture with a wide pore diameter of ~20 Å, presumably representing the active conformation. The overall structure is substantially different from that of the isoform CALHM2, which forms both undecameric hemichannels and gap junctions. The N-terminal small helix folds back to the pore and forms an antiparallel interaction with transmembrane helix 1. Structural analysis revealed that the extracellular loop 1 region within the dimer interface may contribute to oligomeric assembly. A positive potential belt inside the pore was identified that may modulate ion permeation. Our structure offers insights into the assembly and gating mechanism of the CALHM1 channel.