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

ABSTRACT: 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

SUBMITTER: Jirasko V 

PROVIDER: S-EPMC7986703 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature