6DCA

Fab/epitope complex of mouse monoclonal antibody 6B2 targeting a non-phosphorylated tau epitope.

Summary for 6DCA

• Entry DOI: 10.2210/pdb6dca/pdb
• Descriptor: Fab light chain, Fab heavy chain, Microtubule-associated protein tau, ... (5 entities in total)
• Functional Keywords: monoclonal antibody, fab, tau, phosphorylation state-specific antibody, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 12
• Total formula weight: 204764.04

Authors

Chukwu, J.E.,Kong, X.-P. (deposition date: 2018-05-04, release date: 2019-03-20, Last modification date: 2024-10-16)

Primary citation

Chukwu, J.E.,Congdon, E.E.,Sigurdsson, E.M.,Kong, X.P.
Structural characterization of monoclonal antibodies targeting C-terminal Ser404region of phosphorylated tau protein.
MAbs, 11:477-488, 2019

PubMed Abstract: Targeting tau with immunotherapies is currently the most common approach taken in clinical trials of patients with Alzheimer's disease. The most prominent pathological feature of tau is its hyperphosphorylation, which may cause the protein to aggregate into toxic assemblies that collectively lead to neurodegeneration. Of the phospho-epitopes, the region around Ser/Ser has received particular attention for therapeutic targeting because of its prominence and stability in diseased tissue. Herein, we present the antigen-binding fragment (Fab)/epitope complex structures of three different monoclonal antibodies (mAbs) that target the pSer tau epitope region. Most notably, these structures reveal an antigen conformation similar to a previously described pathogenic tau epitope, pSer, which was shown to have a β-strand structure that may be linked to the seeding core in tau oligomers. In addition, we have previously reported on the similarly ordered conformation observed in a pSer epitope, which is in tandem with pSer. Our data are the first Fab structures of mAbs bound to this epitope region of the tau protein and support the existence of proteopathic tau conformations stabilized by specific phosphorylation events that are viable targets for immune modulation.

PubMed: 30794086
DOI: 10.1080/19420862.2019.1574530

Experimental method

X-RAY DIFFRACTION (2.599 Å)