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Cited by 15Cellular transport and secretionAdvanced Electron Microscopy Techniques and ApplicationsImmunotherapy and Immune Responses

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

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Oda, Toshiyuki, Yanagisawa, Haruaki, Shinmori, Hideyuki, Ogawa, Youichi, Kawamura, Tatsuyoshi·2022·eLife
DOI 10.7554/elife.79990PMC PMC9259017

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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.

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Metadata

Authors
Oda, T., Yanagisawa, H., Shinmori, H., Ogawa, Y., & Kawamura, T.
Affiliations
  • University of Yamanashi (JP)
  • The University of Tokyo (JP)
  • University of Yamanashi Hospital (JP)
Corresponding author
Oda, Toshiyuki
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2022-06-27
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.79990
PMC
PMC9259017
OpenAlex
W4283639870
Cited by
15
References
4
Citations by year
2026: 2 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 2
FWCI
1.73
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Japan Society for the Promotion of Science (JP21H02654, JP22H05538)
  • Takeda Science Foundation
  • Daiichi Sankyo Foundation of Life Science
  • Naito Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
Birbeck granules, Langerin, Langerhans cells, honeycomb lattice, C-type lectin, antigen presentation, granule biogenesis, antiviral defense
MeSH terms
Antigens, Surface, Cytoplasmic Granules, Antigens, CD, Lectins, C-Type, Mannose-Binding Lectins, Electron Microscope Tomography

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