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

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 immun...

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Bibliographic Details
Published in:eLife 2022-06, Vol.11
Main Authors: Oda, Toshiyuki, Yanagisawa, Haruaki, Shinmori, Hideyuki, Ogawa, Youichi, Kawamura, Tatsuyoshi
Format: Article
Language:English
Subjects:
Antigen-presenting cells
Binding sites
Birbeck granule
Carbohydrates
Classification
Cryo EM
Crystal structure
Epidermis
Epithelium
Evolution
Granule cells
Health aspects
HIV
Human immunodeficiency virus
immune defense
Immunology and Inflammation
Infections
Internalization
Langerhans cell
Langerhans cells
Lectins
Leprosy
Membrane structure
Microscopy
Mucosa
Pathogens
Structural Biology and Molecular Biophysics
Tomography
Trimers
Virus diseases
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.79990