Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA

Hepatitis C virus infection is a worldwide issue and its NS5A protein interacts with host Cyclophilin A to play a crucial role in viral replication. To date, there is limited structural information for the intrinsically disordered NS5A protein. Here, low-resolution models of NS5A and NS5A-CypA from...

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Main Author: Lee, Jia Jun
Other Authors: Yoon Ho Sup
Format: Theses and Dissertations
Language:English
Published: 2015
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Online Access:http://hdl.handle.net/10356/65353
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-653532023-02-28T18:43:36Z Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA Lee, Jia Jun Yoon Ho Sup School of Biological Sciences DRNTU::Science::Biological sciences::Microbiology::Virology DRNTU::Science::Biological sciences::Biochemistry Hepatitis C virus infection is a worldwide issue and its NS5A protein interacts with host Cyclophilin A to play a crucial role in viral replication. To date, there is limited structural information for the intrinsically disordered NS5A protein. Here, low-resolution models of NS5A and NS5A-CypA from small-angle X-ray scattering data were presented. The models suggest NS5A adopt an extended conformation and binding to CypA may induce NS5A-D1 dimerisation, similar to published data. NS5A-D2 and NS5A-D3 may bind CypA in random coil conformation. Residue P314 of NS5A-D2 is necessary and sufficient for this interaction. The CypA recognition site of NS5A-D2 binds to a region very close to CypA R55 residue, which is responsible for stabilization of the transition state for PPIase activity. A peptide of NS5A-D2 containing the CypA recognition site is able to perturb the conformation of CypA substrate binding cavity and inhibits HCV replication in HCV subgenomic replicon system. ​Master of Science 2015-08-06T04:12:31Z 2015-08-06T04:12:31Z 2015 2015 Thesis Lee, J. J. (2015). Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA. Master's thesis, Nanyang Technological University, Singapore. http://hdl.handle.net/10356/65353 en 88 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences::Microbiology::Virology
DRNTU::Science::Biological sciences::Biochemistry
spellingShingle DRNTU::Science::Biological sciences::Microbiology::Virology
DRNTU::Science::Biological sciences::Biochemistry
Lee, Jia Jun
Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA
description Hepatitis C virus infection is a worldwide issue and its NS5A protein interacts with host Cyclophilin A to play a crucial role in viral replication. To date, there is limited structural information for the intrinsically disordered NS5A protein. Here, low-resolution models of NS5A and NS5A-CypA from small-angle X-ray scattering data were presented. The models suggest NS5A adopt an extended conformation and binding to CypA may induce NS5A-D1 dimerisation, similar to published data. NS5A-D2 and NS5A-D3 may bind CypA in random coil conformation. Residue P314 of NS5A-D2 is necessary and sufficient for this interaction. The CypA recognition site of NS5A-D2 binds to a region very close to CypA R55 residue, which is responsible for stabilization of the transition state for PPIase activity. A peptide of NS5A-D2 containing the CypA recognition site is able to perturb the conformation of CypA substrate binding cavity and inhibits HCV replication in HCV subgenomic replicon system.
author2 Yoon Ho Sup
author_facet Yoon Ho Sup
Lee, Jia Jun
format Theses and Dissertations
author Lee, Jia Jun
author_sort Lee, Jia Jun
title Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA
title_short Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA
title_full Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA
title_fullStr Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA
title_full_unstemmed Structural studies on hepatitis C virus (HCV) NS5A and its molecular interaction with CypA
title_sort structural studies on hepatitis c virus (hcv) ns5a and its molecular interaction with cypa
publishDate 2015
url http://hdl.handle.net/10356/65353
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