| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
We obtain the cryo-electron microscopy structures of Caenorhabditis elegans innexin-6 (INX-6) gap junction channels at atomic resolution. The INX-6 gap junction channel comprises hexadecameric subunits in an open state. The INX-6 structure is highly similar to the human connexin-26 structure, despite the lack of significant sequence similarity. We also have a hemichannel structures of INX-6 in a lipid nanodisc showing that flat double-layer densities obstruct the channel pore. Comparison of the hemichannel structures of a wild-type INX-6 in detergent and nanodisc-reconstituted N-terminal deletion mutant reveal that lipid-mediated N-terminal rearrangement and pore obstruction occur upon nanodisc reconstitution.Together with molecular dynamics simulations and electrophysiology functional assays, our results provide insight into how the large-size pore of gap junction hemichannels can be completely closed in a lipid bilayer.
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