Journal of Molecular Biology
Volume 428, Issue 6, 27 March 2016, Pages 1227-1236
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Hexadecameric structure of an invertebrate gap junction channel

https://doi.org/10.1016/j.jmb.2016.02.011Get rights and content
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Highlights

  • A structure of C. elegans INX-6 was determined by cryo-electron crystallography

  • An INX-6 gap junction channel comprises 16 subunits, a hexadecamer

  • Plug density is observed on the channel pore pathway

  • The oligomeric stoichiometry is different between innexin and connexin

Abstract

Innexins are invertebrate-specific gap junction proteins with four transmembrane helices. These proteins oligomerize to constitute intercellular channels that allow for the passage of small signaling molecules associated with neural and muscular electrical activity. In contrast to the large number of structural and functional studies of connexin gap junction channels, few structural studies of recombinant innexin channels are reported. Here we show the three-dimensional structure of two-dimensionally crystallized Caenorhabditis elegans innexin-6 (INX-6) gap junction channels. The N-terminal deleted INX-6 proteins are crystallized in lipid bilayers. The three-dimensional reconstruction determined by cryo-electron crystallography reveals that a single INX-6 gap junction channel comprises 16 subunits, a hexadecamer, in contrast to chordate connexin channels, which comprise 12 subunits. The channel pore diameters at the cytoplasmic entrance and extracellular gap region are larger than those of connexin26. Two bulb densities are observed in each hemichannel, one in the pore and the other at the cytoplasmic side of the hemichannel in the channel pore pathway. These findings imply a structural diversity of gap junction channels among multicellular organisms.

Abbreviations

INX
innexin
Cx
connexin
GFP
green fluorescent protein
EM
electron microscopy
3D
three-dimensional
2D
two-dimensional
Vj
transjunctional voltage

Keywords

innexin
gap junction channel
cryo-electron crystallography
three-dimensional reconstruction
two-dimensional crystal

Cited by (0)

These authors contribute equally to this work.