Cryo-EM structure of the calcium homeostasis modulator 1 channel.

Abstract:

: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.

journal_name

Sci Adv

journal_title

Science advances

authors

Ren Y,Wen T,Xi Z,Li S,Lu J,Zhang X,Yang X,Shen Y

doi

10.1126/sciadv.aba8161

subject

Has Abstract

pub_date

2020-07-17 00:00:00

pages

eaba8161

issue

29

issn

2375-2548

pii

aba8161

journal_volume

6

pub_type

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