Journal article
Hepatitis C virus sequence divergence preserves p7 viroporin structural and dynamic features
- Abstract:
- The hepatitis C virus (HCV) viroporin p7 oligomerizes to form ion channels, which are required for the assembly and secretion of infectious viruses. The 63-amino acid p7 monomer has two putative transmembrane domains connected by a cytosolic loop, and has both N- and C- termini exposed to the endoplasmic reticulum (ER) lumen. NMR studies have indicated differences between p7 structures of distantly related HCV genotypes. A critical question is whether these differences arise from the high sequence variation between the different isolates and if so, how the divergent structures can support similar biological functions. Here, we present a side-by-side characterization of p7 derived from genotype 1b (isolate J4) in the detergent 6-cyclohexyl-1-hexylphosphocholine (Cyclofos-6) and p7 derived from genotype 5a (isolate EUH1480) in n-dodecylphosphocholine (DPC). The 5a isolate p7 in conditions previously associated with a disputed oligomeric form exhibits secondary structure, dynamics, and solvent accessibility broadly like those of the monomeric 1b isolate p7. The largest differences occur at the start of the second transmembrane domain, which is destabilized in the 5a isolate. The results show a broad consensus among the p7 variants that have been studied under a range of different conditions and indicate that distantly related HCVs preserve key features of structure and dynamics.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.9MB, Terms of use)
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- Publisher copy:
- 10.1038/s41598-019-44413-x
Authors
- Publisher:
- Springer Nature
- Journal:
- Scientific Reports More from this journal
- Volume:
- 9
- Issue:
- 1
- Article number:
- 8383
- Publication date:
- 2019-06-10
- Acceptance date:
- 2019-05-10
- DOI:
- EISSN:
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2045-2322
- Pubs id:
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pubs:997782
- UUID:
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uuid:52de8ea1-b6d5-4aec-8e50-6ded26fec211
- Local pid:
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pubs:997782
- Source identifiers:
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997782
- Deposit date:
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2019-05-13
Terms of use
- Copyright holder:
- Oestringer, BP
- Copyright date:
- 2019
- Notes:
- © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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