9DRQ
Mumps virus fusion glycoprotein F stabilized in prefusion conformation
Summary for 9DRQ
| Entry DOI | 10.2210/pdb9drq/pdb |
| Descriptor | Fusion glycoprotein F0, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | mumps virus, fusion protein, prefusion conformation, vaccine, viral protein |
| Biological source | Mumps orthorubulavirus |
| Total number of polymer chains | 1 |
| Total formula weight | 50203.83 |
| Authors | |
| Primary citation | Loomis, R.J.,Lai, Y.T.,Sowers, S.B.,Fisher, B.,Derrien-Colemyn, A.,Ambrozak, D.R.,Tsybovsky, Y.,Crooke, S.N.,Latner, D.R.,Kong, W.P.,Ruckwardt, T.J.,Plotkin, S.A.,Kwong, P.D.,Mascola, J.R.,Graham, B.S.,Hickman, C.J.,Stewart-Jones, G.B.E. Structure-based design of glycoprotein subunit vaccines for mumps. Proc.Natl.Acad.Sci.USA, 121:e2404053121-e2404053121, 2024 Cited by PubMed Abstract: Mumps virus (MuV) is a highly contagious paramyxovirus that is endemic in most regions of the world and continues to cause outbreaks even in highly immunized populations. Outbreaks of mumps in countries with high measles, mumps, and rubella vaccination coverage have been attributed to waning immunity and antigenic differences between the Jeryl Lynn vaccine strain (genotype A) and circulating wild-type viruses. To obtain a subunit vaccine, we used structure-based design to engineer the mumps fusion (F) glycoprotein stabilized in its prefusion conformation (Pre-F) as well as a chimeric immunogen comprising Pre-F linked to mumps hemagglutinin neuraminidase (HN); in mice, both Pre-F antigen and the chimeric antigen elicited potent cross-reactive plaque reducing neutralizing titers to genotypes A, G, and H mumps. A crystal structure of mumps Pre-F at 2.16 Å resolution validated the stabilization strategy, while a post-fusion form of F was engineered as a comparator. Monoclonal antibodies to mumps Pre-F and HN were isolated from immunized mice; 7 of 14 Pre-F-specific antibodies and 9 of 15 HN-specific antibodies were capable of neutralizing genotype G MuV with a range of potencies. Additionally, 7 of 14 Pre-F-specific antibodies neutralized genotype A mumps. Structural and binding analyses of Pre-F-specific antibodies revealed binding to four discrete neutralizing antigenic sites and binding analyses of HN-specific antibodies revealed binding to five discrete neutralizing antigenic sites. Overall, the PreF and the chimeric Pre-F/HN immunogens are promising candidates to boost MMR-elicited immunity to mumps or as a next-generation vaccine. PubMed: 39527740DOI: 10.1073/pnas.2404053121 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.16 Å) |
Structure validation
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