Two potential therapeutic antibodies bind to a peptide segment of membrane-bound IgE in different conformations.
IgE mediates hypersensitivity reactions responsible for most allergic diseases, which affect 20-40% of the population in developed countries. A 52-residue domain of membrane-bound IgE (mIgE) called CεmX is currently a target for developing therapeutic antibodies; however, its structure is unknown. Here we show that two antibodies with therapeutic potential in IgE-mediated allergic diseases, which can cause cytolytic effects on mIgE-expressing B lymphocytes and downregulate IgE production, target different conformations of an intrinsically disordered region (IDR) in the extracellular CεmX domain. We provide an important example of antibodies targeting an extracellular IDR of a receptor on the surface of intended target cells. We also provide fundamental structural characteristics unique to human mIgE, which may stimulate further studies to investigate whether other monoclonal antibodies (mAbs) targeting intrinsically disordered peptide segments or vaccine-like products targeting IDRs of a membrane protein can be developed.
The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Hsing-Mao
HM
Chu
1] The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan [2] Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
Jon
J
Wright
Fountain Biopharma Inc. Taipei, Taipei 115, Taiwan.
Yueh-Hsuan
YH
Chan
The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Chien-Jen
CJ
Lin
The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Tse Wen
TW
Chang
1] Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan [2] Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan.
Carmay
C
Lim
D000595:Amino Acid Sequence; D001666:Binding Sites, Antibody; D002462:Cell Membrane / Q000276:immunology; D018360:Crystallography, X-Ray; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry / Q000276:immunology*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation
D007073:Immunoglobulin E