5HYS: Structure Of Ige Complexed With Omalizumab

Citation:
Abstract
Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab-Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, in combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. This combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions.
PDB ID: 5HYSDownload
MMDB ID: 139762
PDB Deposition Date: 2016/2/1
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 5HYS: hexameric; determined by author
Molecular Components in 5HYS
Label Count Molecule
Proteins (6 molecules)
2
Epididymis Luminal Protein 214
Molecule annotation
2
Uncharacterized Protein
Molecule annotation
2
IG Epsilon Chain C Region(Gene symbol: IGHE)
Molecule annotation
Chemicals (34 molecules)
1
26
2
4
3
2
4
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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