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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.

SUBMITTER: Ren Y 

PROVIDER: S-EPMC7439498 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Ren Yue Y   Wen Tianlei T   Xi Zhiqin Z   Li Shunjin S   Lu Jing J   Zhang Xing X   Yang Xue X   Shen Yuequan Y  

Science advances 20200717 29


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<sup>2+</sup>-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 substanti  ...[more]

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