8XX0
Crystal structure of anti-IgE antibody HMK-12 Fab complexed with IgE F(ab')2
Summary for 8XX0
| Entry DOI | 10.2210/pdb8xx0/pdb |
| Descriptor | anti-IgE antibody HMK-12 Fab light chain, anti-IgE antibody HMK-12 Fab heavy chain, SPE7 immunoglobulin E F(ab')2 heavy chain, ... (8 entities in total) |
| Functional Keywords | allergy, allosteric, immune system |
| Biological source | Rattus norvegicus (rat) More |
| Total number of polymer chains | 4 |
| Total formula weight | 108240.82 |
| Authors | Hirano, T.,Koyanagi, A.,Kasai, M.,Okumura, K. (deposition date: 2024-01-17, release date: 2024-07-31, Last modification date: 2024-10-30) |
| Primary citation | Hirano, T.,Koyanagi, A.,Ago, H.,Yamamoto, M.,Kitaura, J.,Kasai, M.,Okumura, K. Allosteric inhibition of IgE-Fc epsilon RI interactions by simultaneous targeting of IgE F(ab')2 epitopes. Commun Biol, 7:1042-1042, 2024 Cited by PubMed Abstract: Immunoglobulin E (IgE) plays pivotal roles in allergic diseases through interaction with a high-affinity receptor (FcεRI). We established that Fab fragments of anti-IgE antibodies (HMK-12 Fab) rapidly dissociate preformed IgE-FcεRI complexes in a temperature-dependent manner and inhibit IgE-mediated anaphylactic reactions, even after allergen challenge. X-ray crystallographic studies revealed that HMK-12 Fab interacts with each of two equivalent epitopes on the Cε2 homodimer domain involved in IgE F(ab')2. Consequently, HMK-12 Fab-mediated targeting of Cε2 reduced the binding affinity of Fc domains and resulted in rapid removal of IgE from the receptor complex. This unexpected finding of allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of two epitope sites on the Cε2 homodimer domain of IgE F(ab')2 may have implications for the development of novel therapies for allergic disease. PubMed: 39179708DOI: 10.1038/s42003-024-06633-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
Download full validation report
