Hritz, J. | Search bioRxiv

bioRxiv2026

Structure and epitope mapping of the conformational anti tau antibody DC11

Conformational antibody DC11 was previously shown to discriminate between physiological full length tau proteins and misfolded truncated tau proteins. It was also shown to catalyze in vitro tau aggregation, suggesting a connection with the pre-aggregation conformation of tau proteins. We have crystallized the Fab fragment of the DC11 antibody and characterized its binding with truncated tau proteins using ELISA, NMR and crosslinking mass spectrometry. The presumed model of the complex of DC11 antibody and truncated tau protein was obtained by docking tau321-391 conformations from coarse grained MD simulation into the antibody paratope.

biophysics↗

bioRxiv2023

dGAE(297-391) tau fragment promotes formation of CTE-like full-length tau filaments

The microtubule-associated protein tau forms disease-specific filamentous aggregates in several different neurodegenerative diseases. In order to understand how tau undergoes misfolding into a specific filament type and to control this process for drug development purposes, it is crucial to study in vitro tau aggregation methods and investigate the structures of the obtained filaments at the atomic level. Here, we used the tau fragment dGAE, which aggregates spontaneously, to seed the formation of full-length tau filaments. The structures of dGAE and full-length tau filaments were investigated by solid-state MAS NMR, showing that dGAE allows propagation of a chronic traumatic encephalopathy (CTE)-like fold to the full-length tau. The obtained filaments efficiently seeded tau aggregation in HEK293T cells. This work demonstrates that in vitro preparation of disease-specific types of full-length tau filaments is feasible.

biophysics↗