Inter-domain interactions of TDP-43 as decoded by NMR.
Biochem Biophys Res Commun
; 473(2): 614-9, 2016 Apr 29.
Article
em En
| MEDLINE
| ID: mdl-27040765
ABSTRACT
TDP-43 inclusions have been found in â¼97% ALS as well as an increasing spectrum of other neurodegenerative diseases including Alzheimer's. TDP-43 contains an ubiquitin-like fold, two RRMs and a prion-like domain, but whether they interact with each other remains unknown due to being intrinsically aggregation-prone. Nevertheless, this knowledge is pivotal to understanding physiological functions and pathological roles of TDP-43. Here as facilitated by our previous discovery which allowed NMR characterization of TDP-43 and its five dissected fragments, we successfully decoded that TDP-43 does have dynamic inter-domain interactions, which are coordinated by the intrinsically-disordered prion-like domain. Thus, TDP-43 appears to undergo conformational exchanges between "closed" and "open" states which are needed for its functions. Our study thus offers a mechanism by which cellular processes might control TDP-43 physiology and proteinopathy by mediating its inter-domain interactions.
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Base de dados:
MEDLINE
Assunto principal:
Ressonância Magnética Nuclear Biomolecular
/
Proteínas de Ligação a DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article