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.

本研究中，我们设计了一种登革热病毒外壳蛋白（DENVC）突变体，其中α4-螺旋中的赖氨酸85所赋予的强正电荷区域被半胱氨酸残基所取代，从而消除了正电荷并限制了通过形成二硫键交联的分子间运动。我们证明了该突变体能够在溶液中自我组装成外壳，而不需要核酸。利用圆二色光谱（CD）、差示扫描量热法（DSC）和化学变性等生物物理技术，我们研究了外壳组装的热力学，结果表明，高效的组装与由于α4/α4'运动限制而导致的DENVC稳定性的增加有关。