7YTC

Cryo-EM structure of human FcmR bound to IgM-Fc/J

7YTC の概要

• エントリーDOI: 10.2210/pdb7ytc/pdb
• EMDBエントリー: 34085
• 分子名称: Immunoglobulin heavy constant mu, Immunoglobulin J chain, Fas apoptotic inhibitory molecule 3, ... (4 entities in total)
• 機能のキーワード: immunoglobin m, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 285757.89

構造登録者

Li, Y.,Shen, H.,Xiao, J. (登録日: 2022-08-14, 公開日: 2023-02-01, 最終更新日: 2025-06-25)

主引用文献

Li, Y.,Shen, H.,Zhang, R.,Ji, C.,Wang, Y.,Su, C.,Xiao, J.
Immunoglobulin M perception by Fc mu R.
Nature, 615:907-912, 2023

PubMed Abstract: Immunoglobulin M (IgM) is the first antibody to emerge during embryonic development and the humoral immune response. IgM can exist in several distinct forms, including monomeric, membrane-bound IgM within the B cell receptor (BCR) complex, pentameric and hexameric IgM in serum and secretory IgM on the mucosal surface. FcμR, the only IgM-specific receptor in mammals, recognizes different forms of IgM to regulate diverse immune responses. However, the underlying molecular mechanisms remain unknown. Here we delineate the structural basis of the FcμR-IgM interaction by crystallography and cryo-electron microscopy. We show that two FcμR molecules interact with a Fcμ-Cμ4 dimer, suggesting that FcμR can bind to membrane-bound IgM with a 2:1 stoichiometry. Further analyses reveal that FcμR-binding sites are accessible in the context of IgM BCR. By contrast, pentameric IgM can recruit four FcμR molecules to bind on the same side and thereby facilitate the formation of an FcμR oligomer. One of these FcμR molecules occupies the binding site of the secretory component. Nevertheless, four FcμR molecules bind to the other side of secretory component-containing secretory IgM, consistent with the function of FcμR in the retrotransport of secretory IgM. These results reveal intricate mechanisms of IgM perception by FcμR.

PubMed: 36949194
DOI: 10.1038/s41586-023-05835-w

実験手法

ELECTRON MICROSCOPY (3.39 Å)