C-Terminal Auto-Regulatory Motif of Hepatitis C Virus NS5B Interacts with Human VAPB-MSP to Form a Dynamic Replication Complex

PloS One
Garvita Gupta, Jianxing Song

Abstract

Hepatitis C virus (HCV) is a pathogen of global importance and nearly 200 million people are chronically infected with HCV. HCV is an enveloped single-stranded RNA virus, which is characteristic of the formation of the host membrane associated replication complex. Previous functional studies have already established that the human ER-anchored VAPB protein acts as a host factor to form a complex with HCV NS5A and NS5B, which may be established as a drug target. However, there is lacking of biophysical characterization of the structures and interfaces of the complex, partly due to the dynamic nature of the complex formation and dissociation, which is extensively involved in intrinsically-disordered domains. Here by an integrated use of domain dissection and NMR spectroscopy, for the first time we have successfully deciphered that the HCV NS5B utilizes its auto-regulatory C-linker to bind the VAPB-MSP domain to form a dynamic complex. This finding implies that the NS5B C-linker is capable of playing dual roles by a switch between the folded and disordered states. Interestingly, our previous and present studies together reveal that both HCV NS5A and NS5B bind to the MSP domains of the dimeric VAP with significantly overlapped inter...Continue Reading

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Citations

Jan 31, 2017·Current Opinion in Infectious Diseases·Hans Helmut NillerJanos Minarovits
Apr 4, 2021·Viruses·Hui-Chun LiShih-Yen Lo
Aug 10, 2021·World Journal of Gastroenterology : WJG·Hui-Chun LiShih-Yen Lo
Aug 28, 2021·Cells·Nica BorgeseFrancesca Navone

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Methods Mentioned

BETA
NMR
size exclusion chromatography
dissection

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