Creutznacher, Robert;
Maass, Thorben;
Dülfer, Jasmin;
Feldmann, Clara;
Hartmann, Veronika;
Lane, Miranda Sophie;
Knickmann, Jan;
... Peters, Thomas; + view all
(2022)
Distinct dissociation rates of murine and human norovirus P-domain dimers suggest a role of dimer stability in virus-host interactions.
Communications Biology
, 5
, Article 563. 10.1038/s42003-022-03497-4.
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Abstract
Norovirus capsids are icosahedral particles composed of 90 dimers of the major capsid protein VP1. The C-terminus of the VP1 proteins forms a protruding (P)-domain, mediating receptor attachment, and providing a target for neutralizing antibodies. NMR and native mass spectrometry directly detect P-domain monomers in solution for murine (MNV) but not for human norovirus (HuNoV). We report that the binding of glycochenodeoxycholic acid (GCDCA) stabilizes MNV-1 P-domain dimers (P-dimers) and induces long-range NMR chemical shift perturbations (CSPs) within loops involved in antibody and receptor binding, likely reflecting corresponding conformational changes. Global line shape analysis of monomer and dimer cross-peaks in concentration-dependent methyl TROSY NMR spectra yields a dissociation rate constant koff of about 1 s-1 for MNV-1 P-dimers. For structurally closely related HuNoV GII.4 Saga P-dimers a value of about 10-6 s-1 is obtained from ion-exchange chromatography, suggesting essential differences in the role of GCDCA as a cofactor for MNV and HuNoV infection.
| Type: | Article |
|---|---|
| Title: | Distinct dissociation rates of murine and human norovirus P-domain dimers suggest a role of dimer stability in virus-host interactions |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s42003-022-03497-4 |
| Publisher version: | https://doi.org/10.1038/s42003-022-03497-4 |
| Language: | English |
| Additional information: | s 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. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. |
| Keywords: | Animals, Humans, Mice, Norovirus, Capsid, Caliciviridae Infections, Capsid Proteins, Host Microbial Interactions |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10150317 |
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