RT Journal Article
SR Electronic
T1 Cryo-EM structure of the calcium homeostasis modulator 1 channel
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaba8161
DO 10.1126/sciadv.aba8161
VO 6
IS 29
A1 Ren, Yue
A1 Wen, Tianlei
A1 Xi, Zhiqin
A1 Li, Shunjin
A1 Lu, Jing
A1 Zhang, Xing
A1 Yang, Xue
A1 Shen, Yuequan
YR 2020
UL http://advances.sciencemag.org/content/6/29/eaba8161.abstract
AB 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 Ca2+-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.