8YVU

structure of Ige receptor

8YVU の概要

• エントリーDOI: 10.2210/pdb8yvu/pdb
• EMDBエントリー: 39614
• 分子名称: High affinity immunoglobulin epsilon receptor subunit alpha, High affinity immunoglobulin epsilon receptor subunit beta, High affinity immunoglobulin epsilon receptor subunit gamma, ... (4 entities in total)
• 機能のキーワード: immunology, ige receptor, allergy, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 62352.90

構造登録者

Chen, M.Y.,Su, Q.,Shi, Y.G. (登録日: 2024-03-29, 公開日: 2024-11-06, 最終更新日: 2025-07-23)

主引用文献

Chen, M.,Su, Q.,Shi, Y.
Molecular mechanism of IgE-mediated Fc epsilon RI activation.
Nature, 637:453-460, 2025

PubMed Abstract: Allergic diseases affect more than a quarter of individuals in industrialized countries, and are a major public health concern. The high-affinity Fc receptor for immunoglobulin E (FcεRI), which is mainly present on mast cells and basophils, has a crucial role in allergic diseases. Monomeric immunoglobulin E (IgE) binding to FcεRI regulates mast cell survival, differentiation and maturation. However, the underlying molecular mechanism remains unclear. Here we demonstrate that prior to IgE binding, FcεRI exists mostly as a homodimer on human mast cell membranes. The structure of human FcεRI confirms the dimeric organization, with each promoter comprising one α subunit, one β subunit and two γ subunits. The transmembrane helices of the α subunits form a layered arrangement with those of the γ and β subunits. The dimeric interface is mediated by a four-helix bundle of the α and γ subunits at the intracellular juxtamembrane region. Cholesterol-like molecules embedded within the transmembrane domain may stabilize the dimeric assembly. Upon IgE binding, the dimeric FcεRI dissociates into two protomers, each of which binds to an IgE molecule. This process elicits transcriptional activation of Egr1, Egr3 and Ccl2 in rat basophils, which can be attenuated by inhibiting the FcεRI dimer-to-monomer transition. Collectively, our study reveals the mechanism of antigen-independent, IgE-mediated FcεRI activation.

PubMed: 39442557
DOI: 10.1038/s41586-024-08229-8

実験手法

ELECTRON MICROSCOPY (3.9 Å)