5K6C: Crystal Structure Of Prefusion-stabilized Rsv F Single-chain 9-10 Ds- Cav1 Variant

Citation:
Abstract
Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses. The resultant second-generation 'DS2'-stabilized immunogens have their F subunits genetically linked, their fusion peptides deleted and their interprotomer movements stabilized by an additional disulfide bond. These DS2 immunogens are promising vaccine candidates with superior attributes, such as their lack of a requirement for furin cleavage and their increased antigenic stability against heat inactivation. The iterative structure-based improvement described here may have utility in the optimization of other vaccine antigens.
PDB ID: 5K6CDownload
MMDB ID: 143998
PDB Deposition Date: 2016/5/24
Updated in MMDB: 2016/10
Experimental Method:
x-ray diffraction
Resolution: 3.58  Å
Source Organism:
Similar Structures:
Biological Unit for 5K6C: trimeric; determined by author and by software (PISA)
Molecular Components in 5K6C
Label Count Molecule
Proteins (3 molecules)
3
Fusion Glycoprotein F0,fusion Glycoprotein F0
Molecule annotation
Chemicals (3 molecules)
1
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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