Cryo-electron tomography of Birbeck granules reveals the molecular mechanism of langerin lattice formation
- University of Yamanashi, Japan
- University of Tokyo, Japan
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.
Article and author information
Author details
Haruaki Yanagisawa
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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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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