8YVU

structure of Ige receptor

Summary for 8YVU

• Entry DOI: 10.2210/pdb8yvu/pdb
• EMDB information: 39614
• Descriptor: 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)
• Functional Keywords: immunology, ige receptor, allergy, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 62352.90

Authors

Chen, M.Y.,Su, Q.,Shi, Y.G. (deposition date: 2024-03-29, release date: 2024-11-06, Last modification date: 2025-07-23)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.9 Å)