Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | Structures of ΔD421 Truncated Tau Fibrils. |
|---|---|
| Journal, issue, pages | J Mol Biol, Vol. 437, Issue 10, Page 169051, Year 2025 |
| Publish date | Feb 26, 2025 |
 Authors | Nadia El Mammeri / Pu Duan / Mei Hong /  |
| PubMed Abstract | The microtubule-associated protein tau aggregates into pathological β-sheet amyloid fibrils in Alzheimer's disease (AD) and other neurodegenerative diseases. In these aggregates, tau is chemically ...The microtubule-associated protein tau aggregates into pathological β-sheet amyloid fibrils in Alzheimer's disease (AD) and other neurodegenerative diseases. In these aggregates, tau is chemically modified, including abnormal hyperphosphorylation and truncation. Truncation after D421 in the C-terminal domain occurs at early stages of AD. Here we investigate the structures of ΔD421-truncated 0N4R tau fibrils assembled in vitro in the absence of anionic cofactors. Using solid-state NMR spectroscopy and cryoelectron microscopy, we show that ΔD421-truncated 0N4R tau forms homogeneous fibrils whose rigid core adopts a three-layered β-sheet structure that spans R2, R3 and R4 repeats. This structure is essentially identical to that of full-length tau containing phospho-mimetic mutations at the PHF1 epitope in the C-terminal domain. In comparison, a ΔD421-truncated tau that additionally contains three phospho-mimetic mutations at the AT8 epitope in the proline-rich region forms a fibril core that includes the first half of the C-terminal domain, which is excluded from all known pathological tau fibril cores. These results indicate that the posttranslational modification code of tau contains redundancy: both charge modification and truncation of the C-terminal domain promote a three-layered β-sheet structure, which resembles pathological four-repeat tau structures in several tauopathies. In comparison, reducing the positive charges at the AT8 epitope in ΔD421-truncated tau promotes a fibril core that includes an immobilized C-terminal domain. The absence of this structure in tauopathy brains implies that ΔD421 truncation does not occur in conjunction with AT8 phosphorylation in diseased brains. |
 External links | J Mol Biol / PubMed:40021051 |
| Methods | EM (helical sym.) |
| Resolution | 2.9 Å |
| Structure data | EMDB-48555, PDB-9mr8: |
| Source |
|
 Keywords | STRUCTURAL PROTEIN / Tau / amyloid fibrils |
Escherichia coli (E. coli)
homo sapiens (human)