Summary for 9G13
| Entry DOI | 10.2210/pdb9g13/pdb |
| Descriptor | VHH H3-2, Isoform Tau-F of Microtubule-associated protein tau (3 entities in total) |
| Functional Keywords | vhh, nanobody, tau, immune system |
| Biological source | Lama glama More |
| Total number of polymer chains | 8 |
| Total formula weight | 63678.48 |
| Authors | Dupre, E.,Landrieu, I.,Danis, C.,Hanoulle, X.,Mortelecque, J. (deposition date: 2024-07-09, release date: 2024-07-31, Last modification date: 2025-04-09) |
| Primary citation | Danis, C.,Dupre, E.,Bouillet, T.,Denechaud, M.,Lefebvre, C.,Nguyen, M.,Mortelecque, J.,Cantrelle, F.X.,Rain, J.C.,Hanoulle, X.,Colin, M.,Buee, L.,Landrieu, I. Inhibition of tau neuronal internalization using anti-tau single domain antibodies. Nat Commun, 16:3162-3162, 2025 Cited by PubMed Abstract: In Alzheimer's disease, tau pathology spreads across brain regions as the disease progresses. Intracellular tau can be released and taken up by nearby neurons. We evaluated single domain anti-tau antibodies, also called VHHs, as inhibitors of tau internalization. We identified three VHH inhibitors of tau uptake: A31, H3-2, and Z70. These VHHs compete with the membrane protein LRP1, a major receptor mediating neuronal uptake of tau. A31 and Z70 bind to microtubule binding domain repeats, which are involved in the interaction with LRP1. VHH H3-2 is the only VHH from our library that reduces the internalization of both monomeric tau and tau fibrils. VHH H3-2 binds a C-terminal tau epitope with high affinity. Its three-dimensional structure in complex with a tau peptide reveals a unique binding mode as a VHH-swapped dimer. These anti-tau VHHs are interesting tools to study tau prion-like propagation in tauopathies and potentially develop novel biotherapies. PubMed: 40175345DOI: 10.1038/s41467-025-58383-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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