Article ; Online: NMR Relaxation Experiments Probe Monomer-Fibril Interaction and Identify Critical Interacting Residues Responsible for Distinct Tau Fibril Morphologies.
The journal of physical chemistry letters
2023 Volume 14, Issue 29, Page(s) 6583–6591
Abstract: Tau aggregation is governed by secondary processes, a major pathological pathway for tau protein fibril propagation, yet its molecular mechanism remains unknown. This work uses saturation transfer and lifetime line-broadening experiments to identify the ... ...
| Abstract | Tau aggregation is governed by secondary processes, a major pathological pathway for tau protein fibril propagation, yet its molecular mechanism remains unknown. This work uses saturation transfer and lifetime line-broadening experiments to identify the critical residues involved in these secondary processes. Distinct residue-specific NMR relaxation parameters were obtained for the truncated three repeat tau construct (K19) in equilibrium with structurally different, self-aggregated (saK19) or heparin-induced (hK19) fibrils. The interacting residues are restricted to R3 repeat for hK19 and to R3, R4, and R' repeats for saK19 fibrils. Furthermore, the relaxation profiles of tau monomers in equilibrium with the structurally comparable, in vitro pathological fibrils (tauAD and tauCTE) were similar but distinct from hK19 or saK19 fibrils. Thus, residue-specific relaxation identifies the important residues involved in the binding of monomers to the fibrils. The relaxation profile of the monomers in equilibrium with the NMR invisible fibril seeds potentially distinguishes the distinct structures of tau fibrils. |
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| MeSH term(s) | tau Proteins/chemistry ; Amino Acid Sequence ; Magnetic Resonance Spectroscopy ; Magnetic Resonance Imaging ; Amyloid/chemistry |
| Chemical Substances | tau Proteins ; Amyloid |
| Language | English |
| Publishing date | 2023-07-17 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 1948-7185 |
| ISSN (online) | 1948-7185 |
| DOI | 10.1021/acs.jpclett.3c00912 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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