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Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
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Hepatitis C virus sequence divergence preserves p7 viroporin structural and dynamic features.
Benjamin P Oestringer1,2,3, Juan H Bolivar1, Jolyon K Claridge2,4,5
1Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom.
Scientific Reports
|June 12, 2019
Summary
Hepatitis C virus (HCV) p7 protein structures from different genotypes show conserved features. Despite sequence variations, distantly related HCVs maintain essential structural and dynamic characteristics for viral function.
Area of Science:
- Virology
- Structural Biology
- Membrane Protein Biophysics
Background:
- The hepatitis C virus (HCV) p7 protein is a viroporin essential for viral assembly and release.
- HCV p7 oligomerizes into ion channels, with a structure featuring two transmembrane domains and a cytosolic loop.
- Previous NMR studies revealed structural differences between p7 from various HCV genotypes.
Purpose of the Study:
- To investigate if sequence variations in HCV p7 explain structural differences between genotypes.
- To compare the structure and dynamics of p7 from genotype 1b and genotype 5a.
- To determine how divergent p7 structures support similar biological functions.
Main Methods:
- Side-by-side characterization of p7 from genotype 1b (J4 isolate) in Cyclofos-6 detergent.
- Characterization of p7 from genotype 5a (EUH1480 isolate) in DPC detergent.
- Analysis of secondary structure, dynamics, and solvent accessibility using biophysical techniques.
Main Results:
- HCV p7 from genotype 5a exhibited secondary structure, dynamics, and solvent accessibility similar to monomeric genotype 1b p7.
- The most significant structural differences were observed at the beginning of the second transmembrane domain in the 5a isolate, showing destabilization.
- A broad consensus in structural and dynamic features was found among studied p7 variants across different conditions.
Conclusions:
- Distantly related HCV genotypes preserve key structural and dynamic features in the p7 protein.
- Despite sequence variation, conserved structural elements likely underpin the conserved biological functions of p7.
- The findings suggest a conserved mechanism for p7 ion channel formation and function across diverse HCV genotypes.
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