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

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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

1. Oda T
2. Yanagisawa H
(2022) Structure of human langerin complex in Birbeck granules
7WZ8.

https://doi.org/10.2210/pdb7WZ8/pdb

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0001-8090-2159
Haruaki Yanagisawa

Department of Cell Biology and Anatomy, University of Tokyo, Tokyo, Japan

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0313-2343
Hideyuki Shinmori

Faculty of Life and Environmental Science, University of Yamanashi, Yamanashi, Japan

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9864-8371
Youichi Ogawa

Department of Dermatology, University of Yamanashi, Yamanashi, Japan

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2635-888X
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.

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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.