1. Structural Biology and Molecular Biophysics
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Cryo-EM structures and functional properties of CALHM channels of the human placenta

  1. Katarzyna Drożdżyk
  2. Marta Sawicka  Is a corresponding author
  3. Maria-Isabel Bahamonde-Santos
  4. Zaugg Jonas
  5. Dawid Deneka
  6. Christiane Albrecht
  7. Raimund Dutzler  Is a corresponding author
  1. University of Zürich, Switzerland
  2. University of Bern, Switzerland
Research Article
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Cite this article as: eLife 2020;9:e55853 doi: 10.7554/eLife.55853

Abstract

The transport of substances across the placenta is essential for the development of the fetus. Here, we were interested in the role of channels of the calcium homeostasis modulator (CALHM) family in the human placenta. By transcript analysis, we found the paralogs CALHM2, 4, and 6 to be highly expressed in this organ and upregulated during trophoblast differentiation. Based on electrophysiology, we found that activation of these paralogs differs from the voltage- and calcium-gated channel CALHM1. Cryo-EM structures of CALHM4 display decameric and undecameric assemblies with large cylindrical pore, while in CALHM6 a conformational change has converted the pore shape into a conus that narrows at the intracellular side, thus describing distinct functional states of the channel. The pore geometry alters the distribution of lipids, which occupy the cylindrical pore of CALHM4 in a bilayer-like arrangement whereas they have redistributed in the conical pore of CALHM6 with potential functional consequences.

Data availability

cryo-EM data were deposited with the PDB and cryo-EM densiities were deposited with the Electron Microscopy databank

The following data sets were generated

Article and author information

Author details

  1. Katarzyna Drożdżyk

    Department of Biochemistry, University of Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6288-4735
  2. Marta Sawicka

    Department of Biochemistry, University of Zürich, Zürich, Switzerland
    For correspondence
    m.sawicka@bioc.uzh.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4589-4290
  3. Maria-Isabel Bahamonde-Santos

    Department of Biochemistry, University of Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Zaugg Jonas

    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Dawid Deneka

    Department of Biochemistry, University of Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Christiane Albrecht

    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Raimund Dutzler

    Department of Biochemistry, University of Zürich, Zürich, Switzerland
    For correspondence
    dutzler@bioc.uzh.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2193-6129

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_163421)

  • Raimund Dutzler

Stiftung Lindenhof Bern

  • Christiane Albrecht

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Human placental tissues were collected from the Division of Obstetrics and Gynecology, Lindenhofgruppe Bern, Switzerland, under approval by the ethical commission of the Canton of Bern (approval No Basec 2016-00250). Written informed consent was obtained from all participants.

Reviewing Editor

  1. Kenton J Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Publication history

  1. Received: February 7, 2020
  2. Accepted: May 5, 2020
  3. Accepted Manuscript published: May 6, 2020 (version 1)
  4. Version of Record published: May 21, 2020 (version 2)

Copyright

© 2020, Drożdżyk et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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