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Structure of the connexin 26 gap junction channel at 3.5 Å resolution

Nature volume 458, pages 597–602 (2009)Cite this article

Abstract

Gap junctions consist of arrays of intercellular channels between adjacent cells that permit the exchange of ions and small molecules. Here we report the crystal structure of the gap junction channel formed by human connexin 26 (Cx26, also known as GJB2) at 3.5 Å resolution, and discuss structural determinants of solute transport through the channel. The density map showed the two membrane-spanning hemichannels and the arrangement of the four transmembrane helices of the six protomers forming each hemichannel. The hemichannels feature a positively charged cytoplasmic entrance, a funnel, a negatively charged transmembrane pathway, and an extracellular cavity. The pore is narrowed at the funnel, which is formed by the six amino-terminal helices lining the wall of the channel, which thus determines the molecular size restriction at the channel entrance. The structure of the Cx26 gap junction channel also has implications for the gating of the channel by the transjunctional voltage.

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Figure 1: Overall structure of the Cx26 gap junction channel in ribbon representation.
Figure 2: Stereo view of the Cx26 protomer in ribbon representation.
Figure 3: Molecular architecture of the Cx26 gap junction channel.
Figure 4: Pore structure of the Cx26 gap junction channel.
Figure 5: Structure of the pore funnel.

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Accession codes

Primary accessions

Protein Data Bank

Data deposits

The atomic coordinate and the structure factor for the reported crystal structure have been deposited with the Protein Data Bank under accession code 2ZW3.

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Acknowledgements

We thank T. Tomizaki for help in the diffraction data collection on X06SA at the Swiss Light Source. This work was supported by Grants-in-Aid for Scientific Research (10687101, 16087206 and 18207006) and the GCOE program (A-041) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T.T.), the Japan Biological Informatics Consortium (to T.T.), the Strategic Japan-UK Cooperation Program of the Japan Science and Technology Agency (to T.T.), and Grants-in-Aid for Specially Promoted Research (to Y.F.) and the New Energy and Industrial Technology Development Organization (to Y.F.). We thank T. Walz for critical reading of this manuscript.

Author Contributions S.M., S.N., M.S., E.Y. and T.T. performed X-ray structural analysis. S.M., A.O., Y.F. and T.T. wrote the paper.

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Authors and Affiliations

  1. Institute for Protein Research, Osaka University, OLABB, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan ,

    Shoji Maeda, So Nakagawa, Michihiro Suga, Eiki Yamashita & Tomitake Tsukihara

  2. Department of Biophysics, Graduate School of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan,

    Atsunori Oshima & Yoshinori Fujiyoshi

  3. Picobiology Institute, Graduate School of Life Science, University of Hyogo, Kamigohori, Akoh, Hyogo 678-1297, Japan ,

    Tomitake Tsukihara

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Correspondence to Tomitake Tsukihara.

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Maeda, S., Nakagawa, S., Suga, M. et al. Structure of the connexin 26 gap junction channel at 3.5 Å resolution. Nature 458, 597–602 (2009). https://doi.org/10.1038/nature07869

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