Inter-domain interactions of TDP-43 as decoded by NMR.
Related Articles Inter-domain interactions of TDP-43 as decoded by NMR.
Biochem Biophys Res Commun. 2016 Apr 29;473(2):614-9
Authors: Wei Y, Lim L, Wang L, Song J
Abstract
TDP-43 inclusions have been found in ~97% 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.
PMID: 27040765 [PubMed - indexed for MEDLINE]
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