English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Significance DNA sequence variants in theTbk1 gene associate with both sporadic and familial amyotrophic lateral sclerosis (ALS). We report a functional study of 25 missense TBK1 mutations scattered across all structural domains. These mutations negatively impact TBK1 functions ranging from kinase activity, substrate specificity, dimerization, and protein stability to interactions with critical autophagy receptors. Contrary to previous studies, we find that TBK1 dimerization increases protein stability and improves catalytic efficiency, but it is not required for its activation. Our results show that different TBK1 ALS mutations, which are associated with the same pathological outcome, affect distinct signaling pathways in which TBK1 is critically involved. TBK1-associated ALS provides a remarkable example of the genetic and functional complexity of ALS disease mechanisms.

Effects of ALS-associated TANK binding kinase 1 mutations on protein–protein interactions and kinase activity