6LRA

The complex structure of PHF core domain peptide of tau and antibody's Fab domain.

Summary for 6LRA

• Entry DOI: 10.2210/pdb6lra/pdb
• Descriptor: Fab Heavy Chain, Fab Light Chain, VQIINK, ... (4 entities in total)
• Functional Keywords: tauopathies, tau protein, antibody, alzheimer's disease, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 47534.98

Authors

Tomohiro, T.,Kouki, S.,Tomohiro, S.,Takahiro, T.,Katsushiro, M.,Yasuko, I.,Katsuhiko, M.,Taizo, T.,Toshimitsu, I.,Koji, T. (deposition date: 2020-01-15, release date: 2020-08-26, Last modification date: 2024-11-13)

Primary citation

Tsuchida, T.,Susa, K.,Kibiki, T.,Tsuchiya, T.,Miyamoto, K.,In, Y.,Minoura, K.,Taniguchi, T.,Ishida, T.,Tomoo, K.
Crystal structure of the human tau PHF core domain VQIINK complexed with the Fab domain of monoclonal antibody Tau2r3.
Febs Lett., 2020

PubMed Abstract: Neurofibrillary tangles formed by abnormally aggregated tau protein are a histopathological feature of tauopathies. A tau aggregation inhibitor is a potential therapeutic agent for tauopathies. In this study, we prepared a monoclonal antibody for tau, monoclonal antibody to tau protein (Tau2r3), using as epitope the GGKVQIINKKLD peptide in the microtubule-binding domain of tau, the key region mediating tau aggregation. We show that Tau2r3 clearly inhibits tau aggregation. To analyze the inhibition mechanism of Tau2r3, we solved the crystal structure of the Fab domain of Tau2r3 (Fab2r3) in complex with the VQIINK peptide. In the Fab2r3-VQIINK structure, the second and sixth polar residues and the fourth hydrophobic residue of VQIINK are crucial for binding to Fab2r3. The structural data for the Fab2r3-VQIINK complex could contribute to the design of new tau aggregation inhibitors.

PubMed: 32282060
DOI: 10.1002/1873-3468.13791

Experimental method

X-RAY DIFFRACTION (1.9 Å)