Interaction kinetics reveal distinct properties of conformational ensembles of three-repeat and four-repeat tau proteins.
aggregation
conformational ensemble
crosslinking mass spectrometry
intrinsically disordered proteins
microscale thermophoresis
surface plasmon resonance
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
23
02
2022
received:
24
11
2021
accepted:
10
03
2022
pubmed:
25
3
2022
medline:
20
5
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
Tau protein is an intrinsically disordered protein. Its physiological state is best described as a conformational ensemble (CE) of metastable structures interconverting on the local and molecular scale. The monoclonal antibody DC39C recognizes a linear C-terminal tau epitope, and as the tau interaction partner, its binding parameters report about tau CE. Association kinetics of DC39C binding, together with crosslinking mass spectrometry, show differences in the accessibility of the C terminus in CEs of tau isoforms. Furthermore, removal of the C terminus accelerated the aggregation kinetics of three-repeat tau proteins. Our results suggest a novel mechanism of splicing-driven regulation of the tau C-terminal domain with consequences on the specific roles of tau isoforms in microtubule assembly and pathological aggregation.
Identifiants
pubmed: 35322890
doi: 10.1002/1873-3468.14339
doi:
Substances chimiques
Intrinsically Disordered Proteins
0
Protein Isoforms
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1178-1189Informations de copyright
© 2022 Federation of European Biochemical Societies.
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