1. Immunology and Inflammation
  2. Structural Biology and Molecular Biophysics

Cryo-electron tomography of Birbeck granules reveals the molecular mechanism of langerin lattice formation

  1. Toshiyuki Oda  Is a corresponding author
  2. Haruaki Yanagisawa
  3. Hideyuki Shinmori
  4. Youichi Ogawa
  5. Tatsuyoshi Kawamura
  1. University of Yamanashi, Japan
  2. University of Tokyo, Japan
https://doi.org/10.7554/eLife.79990
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  1. Toshiyuki Oda
  2. Haruaki Yanagisawa
  3. Hideyuki Shinmori
  4. Youichi Ogawa
  5. Tatsuyoshi Kawamura
(2022)
Cryo-electron tomography of Birbeck granules reveals the molecular mechanism of langerin lattice formation
eLife 11:e79990.
https://doi.org/10.7554/eLife.79990
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Abstract

Langerhans cells are specialized antigen-presenting cells localized within the epidermis and mucosal epithelium. Upon contact with Langerhans cells, pathogens are captured by the C-type lectin langerin and internalized into a structurally unique vesicle known as a Birbeck granule. Although the immunological role of Langerhans cells and Birbeck granules have been extensively studied, the mechanism by which the characteristic zippered membrane structure of Birbeck granules is formed remains elusive. In this study, we observed isolated Birbeck granules using cryo-electron tomography and reconstructed the 3D structure of the repeating unit of the honeycomb lattice of langerin at 6.4 Å resolution. We found that the interaction between the two langerin trimers was mediated by docking the flexible loop at residues 258-263 into the secondary carbohydrate-binding cleft. Mutations within the loop inhibited Birbeck granule formation and the internalization of HIV pseudovirus. These findings suggest a molecular mechanism for membrane zippering during Birbeck granule biogenesis and provide insight into the role of langerin in the defense against viral infection.

Data availability

The map and the model have been deposited in EMDB under theaccession numbers: EMD-32906, and PDB 7WZ8.

The following data sets were generated

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Author details

  1. Toshiyuki Oda

    Department of Anatomy and Structural Biology, University of Yamanashi, Yamanashi, Japan
    For correspondence
    toda@yamanashi.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8090-2159

  2. Haruaki Yanagisawa

    Department of Cell Biology and Anatomy, University of Tokyo, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0313-2343

  3. Hideyuki Shinmori

    Faculty of Life and Environmental Science, University of Yamanashi, Yamanashi, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9864-8371

  4. Youichi Ogawa

    Department of Dermatology, University of Yamanashi, Yamanashi, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2635-888X

  5. Tatsuyoshi Kawamura

    Department of Dermatology, University of Yamanashi, Yamanashi, Japan
    Competing interests
    The authors declare that no competing interests exist.

Funding

Japan Society for the Promotion of Science (JP21H02654)

  • Toshiyuki Oda

Takeda Science Foundation

  • Toshiyuki Oda

Daiichi Sankyo Foundation of Life Science

  • Toshiyuki Oda

Naito Foundation

  • Toshiyuki Oda

Japan Society for the Promotion of Science (JP22H05538)

  • Toshiyuki Oda

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

Copyright

© 2022, Oda 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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  1. Toshiyuki Oda
  2. Haruaki Yanagisawa
  3. Hideyuki Shinmori
  4. Youichi Ogawa
  5. Tatsuyoshi Kawamura
(2022)
Cryo-electron tomography of Birbeck granules reveals the molecular mechanism of langerin lattice formation
eLife 11:e79990.
https://doi.org/10.7554/eLife.79990

Share this article

https://doi.org/10.7554/eLife.79990

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