6lyg

Publication Abstract from PubMed

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(2+)-free CALHM1 from Danio rerio at an overall resolution of 3.1 A. Our structure reveals an octameric architecture with a wide pore diameter of ~20 A, 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.

Cryo-EM structure of the calcium homeostasis modulator 1 channel.,Ren Y, Wen T, Xi Z, Li S, Lu J, Zhang X, Yang X, Shen Y Sci Adv. 2020 Jul 17;6(29):eaba8161. doi: 10.1126/sciadv.aba8161. eCollection, 2020 Jul. PMID:32832630^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.