4LKX

Humanized antibody 4B12 Fab complexed with a CemX segment

Summary for 4LKX

• Entry DOI: 10.2210/pdb4lkx/pdb
• Descriptor: Fab fragment heavy chain, Fab fragment light chain, CemX segment, ... (4 entities in total)
• Functional Keywords: immunoglobulin, antibody, fab-peptide complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 49094.73

Authors

Chu, H.M.,Wright, J.,Chan, Y.H.,Lin, C.J.,Chang, T.W.,Lim, C. (deposition date: 2013-07-09, release date: 2014-01-29, Last modification date: 2023-11-08)

Primary citation

Chu, H.M.,Wright, J.,Chan, Y.H.,Lin, C.J.,Chang, T.W.,Lim, C.
Two potential therapeutic antibodies bind to a peptide segment of membrane-bound IgE in different conformations.
Nat Commun, 5:3139-3139, 2014

PubMed Abstract: 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.

PubMed: 24457896
DOI: 10.1038/ncomms4139

Experimental method

X-RAY DIFFRACTION (1.92 Å)