8FNZ

Acetylated tau repeat 1 and 2 fragment (AcR1R2)

Summary for 8FNZ

• Entry DOI: 10.2210/pdb8fnz/pdb
• EMDB information: 28721
• Descriptor: Microtubule-associated protein tau, acetylated repeat 1 and 2 fragment (1 entity in total)
• Functional Keywords: amyloid motif acetylation tau repeat domain post-translational modification, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 48
• Total formula weight: 99520.90

Authors

Li, L.,Nguyen, A.B.,Mullapudi, V.,Joachimiak, L. (deposition date: 2022-12-29, release date: 2023-06-28, Last modification date: 2024-10-23)

Primary citation

Li, L.,Nguyen, B.A.,Mullapudi, V.,Li, Y.,Saelices, L.,Joachimiak, L.A.
Disease-associated patterns of acetylation stabilize tau fibril formation.
Structure, 31:1025-1037.e4, 2023

PubMed Abstract: Assembly of tau into beta-sheet-rich amyloids dictates the pathology of a diversity of diseases. Lysine acetylation has been proposed to drive tau amyloid assembly, but no direct mechanism has emerged. Using tau fragments, we identify patterns of acetylation that flank amyloidogenic motifs on the tau fragments that promote rapid fibril assembly. We determined a 3.9 Å cryo-EM amyloid fibril structure assembled from an acetylated tau fragment uncovering how lysine acetylation can mediate gain-of-function interactions. Comparison of the structure to an ex vivo tauopathy fibril reveals regions of structural similarity. Finally, we show that fibrils encoding disease-associated patterns of acetylation are active in cell-based tau aggregation assays. Our data uncover the dual role of lysine residues in limiting tau aggregation while their acetylation leads to stabilizing pro-aggregation interactions. Design of tau sequence with specific acetylation patterns may lead to controllable tau aggregation to direct folding of tau into distinct amyloid folds.

PubMed: 37348495
DOI: 10.1016/j.str.2023.05.020

Experimental method

ELECTRON MICROSCOPY (3.88 Å)