PDBsum entry 6bb4

Immune system

PDB id: 6bb4

Contents

Protein chains

211 a.a.

216 a.a.

Ligands

ILE-VAL-TYR-LYS-SEP-PRO-VAL ×3

PO4 ×3

Waters ×874

PDB id:

6bb4

Name:

Immune system

Title:

Fab/epitope complex of mouse monoclonal antibody c5.2 targeting a phospho-tau epitope.

Structure:

Mouse monoclonal antibody c5.2 fab light chain. Chain: l, m, n. Mouse monoclonal antibody c5.2 fab heavy chain. Chain: h, i, j. Microtubule-associated protein tau. Chain: p, q, r. Synonym: neurofibrillary tangle protein,paired helical filament-tau, phf-tau. Engineered: yes

Source:

Mus musculus. Organism_taxid: 10090. Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606

Resolution:

2.10Å R-factor: 0.218 R-free: 0.270

Authors:

J.E.Chukwu,X.-P.Kong

Key ref:

J.E.Chukwu et al. (2018). Tau Antibody Structure Reveals a Molecular Switch Defining a Pathological Conformation of the Tau Protein. Sci Rep, 8, 6209. PubMed id: 29670132

Date:

16-Oct-17 Release date: 02-May-18

Protein chains

No UniProt id for this chain

Struc: 211 a.a.

Protein chains

No UniProt id for this chain

Struc: 216 a.a.

Sci Rep 8:6209 (2018)

PubMed id: 29670132

Tau Antibody Structure Reveals a Molecular Switch Defining a Pathological Conformation of the Tau Protein.

J.E.Chukwu, J.T.Pedersen, L.Ã.˜.Pedersen, C.Volbracht, E.M.Sigurdsson, X.P.Kong.

ABSTRACT

Tau antibodies have shown therapeutic potential for Alzheimer's disease and several are in clinical trials. As a microtubule-associated protein, tau relies on dynamic phosphorylation for its normal functions. In tauopathies, it becomes hyperphosphorylated and aggregates into toxic assemblies, which collectively lead to neurodegeneration. Of the phospho-epitopes, the region around Ser396 has received particular attention because of its prominence and stability in tauopathies. Here we report the first structure of a monoclonal tau antibody in complex with the pathologically important phospho-Ser396 residue. Its binding region reveals tau residues Tyr394 to phospho-Ser396 stabilized in a β-strand conformation that is coordinated by a phospho-specific antigen binding site. These details highlight a molecular switch that defines this prominent conformation of tau and ways to target it. Overall, the structure of the antibody-antigen complex clarifies why certain phosphorylation sites in tau are more closely linked to neurodegeneration than others.