Back to Journals » Virus Adaptation and Treatment » Volume 2

Conformations of the monomeric hepatitis C virus RNA-dependent RNA polymerase

Authors Chinnaswamy S, Murali A, Cai H, Yi G, Palaninathan S, Kao C

Published 11 March 2010 Volume 2010:2 Pages 21—39


Review by Single-blind

Peer reviewer comments 3

Sreedhar Chinnaswamy1,2,3, Ayaluru Murali1,3, Hui Cai1, Guanghui Yi1, Satheesh Palaninathan2, C Cheng Kao1

1Interdisciplinary Biochemistry Program, Indiana University, Bloomington, Indiana, USA; 2Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas, USA; 3These authors contributed equally to this work and can be considered co-equal first authors

Abstract: The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) changes its conformation and oligomerization state in association with the steps in RNA synthesis. Using a human right hand as an analogy, the crystal structure of the HCV RdRp has extensive interactions between the “finger” and “thumb” domains which result in a closed conformation. However, the RdRp must form a partially open conformation to accommodate the nascent and template RNA duplex during RNA synthesis, and to interact with the retinoblastoma protein through residues in the “palm” domain. A motif named the Δ1 loop has been previously proposed to regulate the transition from the closed to the open conformation. We used negative-stain electron microscopy and single particle reconstruction to identify several conformations of the HCV RdRp monomer, from closed to open. An RdRp with five amino acids deleted in the tip of the Δ1 loop resulted in an open conformation, confirming the importance of this loop in regulating RdRp conformations. Bioinformatics analysis of HCV strains focusing on the Δ1 loop and its interacting surfaces further defined the requirements for this gating mechanism in the HCV RdRp. These results provide glimpses into the dynamic conformations of the HCV RdRp and should provide insights into alternative conformations of the HCV polymerase that could serve as targets for antiviral development against HCV.

Keywords: hepatitis C virus, RNA-dependent RNA polymerase, single particle reconstruction, conformational change

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF] 


Other articles by this author:

Phosphorylation of the viral coat protein regulates RNA virus infection

Hoover HS, Kao CC

Virus Adaptation and Treatment 2016, 8:13-20

Published Date: 24 November 2016

Mapping protein–RNA interactions

Vaughan R, Running W, Qi R, Kao CC

Virus Adaptation and Treatment 2012, 4:29-41

Published Date: 2 May 2012

Small molecule inhibitors of the SARS-CoV Nsp15 endoribonuclease

J Ortiz-Alcantara, K Bhardwaj, S Palaninathan, et al.

Virus Adaptation and Treatment 2010, 2:125-133

Published Date: 6 September 2010

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Emerging treatment options for the mucopolysaccharidoses

Giugliani R, Federhen A, Silva AA, Bittar CM, de Souza CF, Netto CB, Mayer FQ, Baldo G, Matte U

Research and Reports in Endocrine Disorders 2012, 2:53-64

Published Date: 6 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010