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/

Zendy Plus

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

Zendy Tools

Zendy Open

The Hepatitis C virus nonstructural protein 5A (NS5A) is a membrane‐associated protein involved in multiple steps of the viral life cycle. Direct‐acting antivirals (DAAs) targeting NS5A are a cornerstone of antiviral therapy, but the mode‐of‐action of these drugs is poorly understood. This is due to the lack of information on the membrane‐bound NS5A structure. Herein, we present the structural model of an NS5A AH‐linker‐D1 protein reconstituted as proteoliposomes. We use highly sensitive proton‐detected solid‐state NMR methods suitable to study samples generated through synthetic biology approaches. Spectra analyses disclose that both the AH membrane anchor and the linker are highly flexible. Paramagnetic relaxation enhancements (PRE) reveal that the dimer organization in lipids requires a new type of NS5A self‐interaction not reflected in previous crystal structures. In conclusion, we provide the first characterization of NS5A AH‐linker‐D1 in a lipidic environment shedding light onto the mode‐of‐action of clinically used NS5A inhibitors.

Dimer Organization of Membrane‐Associated NS5A of Hepatitis C Virus as Determined by Highly Sensitive 1 H‐Detected Solid‐State NMR