9G13

VHH H3-2 in complex with Tau C-terminal peptide

これはPDB形式変換不可エントリーです。

9G13 の概要

• エントリーDOI: 10.2210/pdb9g13/pdb
• 分子名称: VHH H3-2, Isoform Tau-F of Microtubule-associated protein tau (3 entities in total)
• 機能のキーワード: vhh, nanobody, tau, immune system
• 由来する生物種: Lama glama; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 63678.48

構造登録者

Dupre, E.,Landrieu, I.,Danis, C.,Hanoulle, X.,Mortelecque, J. (登録日: 2024-07-09, 公開日: 2024-07-31, 最終更新日: 2025-04-09)

主引用文献

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

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: 40175345
DOI: 10.1038/s41467-025-58383-4

実験手法

X-RAY DIFFRACTION (1.8 Å)