Self-assembly of dengue virus empty capsid-like particles in solution. Neves-Martins et al.
Here we designed a dengue virus capsid protein (DENVC) mutant in which a highly positive spot conferred by arginine 85 in α4-helix was replaced by a cysteine residue, simultaneously removing the positive charge and restricting the intermolecular motion through the formation of a disulfide cross-link. We showed that the mutant self-assembles into capsids in solution without nucleic acids. Using biophysical techniques, such as CD, DSC, and chemical denaturation we investigated capsid assembly thermodynamics, showing that an efficient assembly is related to an increased DENVC stability due to α4/α4’ motion restriction.