Dynamic stability of salt stable cowpea chlorotic mottle virus capsid protein dimers and pentamers of dimers

Abstract

Intermediates of the self-assembly process of the salt stable cowpea chlorotic mottle virus (ss-CCMV) capsid can be modelled atomistically on realistic computational timescales either by studying oligomers in equilibrium or by focusing on their dissociation instead of their association. Our previous studies showed that among the three possible dimer interfaces in the icosahedral capsid, two are thermodynamically relevant for capsid formation. The aim of the current study is to evaluate the relative structural stabilities of the three different ss-CCMV dimers and to find and understand the conditions that lead to their dissociation. Long timescale molecular dynamics simulations at 300 K of the various dimers and of the pentamer of dimers underscore the importance of large contact surfaces on stabilizing the capsid subunits within an oligomer. Simulations in implicit solvent show that at higher temperature (350 K), the N-terminal tails of the protein units act as tethers, delaying dissociation for all but the most stable interface. The pentamer of dimers is also found to be stable on long timescales at 300 K, with an inherent flexibility of the outer protein chains.

The diversity of protein-protein interaction interfaces within T=3 icosahedral viral capsids

“…Due to the size and strength of the Leviviridae dimerization interfaces, they are expected to be stronger than the trimerization, hexamerization and pentamerization interfaces, implying that during disassembly, CP2-CP2 interactions will break before interactions within a CP2 dimer (intra-CP2), as was shown in previous acid disassembly experiments ( Stockley et al, 2007 ). In contrast, because of the relative chemical similarity between the dimerization, pentamerization and hexamerization interfaces in jelly-roll viruses, these interactions are likely to break at similar denaturant conditions, while the trimerization interfaces may break in milder conditions ( Szoverfi and Fejer, 2022 ). The swelling of the CCMV capsid by increasing the size of the pore at the trimerization axis ( Speir et al, 1995 ; Tama and Brooks, 2002 ) is in accordance with this observation.…”

Deciphering the Thermal Stability of Bacteriophage MS2-Derived Virus-like Particle and Its Engineered Variant

“…3−5 For efficient biomedical usage, the size of VLPs has also been tuned either by changes in physicochemical conditions such as ionic strength or point mutations. 6,7 Changes in the size of VLPs have an impact on their symmetry and stability. 8 Therefore, it is important to study the stability of VLPs before selecting them as candidates for vaccine or drug delivery formulations.…”

“…In general, the assembly formation of VLPs is driven by the Brownian motion of capsid proteins, intra- or intersubunit interactions, and molecular scaffolds (nucleic acid or anions or packaging signals) together acting as molecular velcro. Self-assembly reduces the free energy of the system by forming a complete and highly symmetric macromolecular assembly. , VLPs offer diverse nanotechnological and biomedical applications, including potential vaccines, and drug or cargo delivery vehicles. − For efficient biomedical usage, the size of VLPs has also been tuned either by changes in physicochemical conditions such as ionic strength or point mutations. , Changes in the size of VLPs have an impact on their symmetry and stability . Therefore, it is important to study the stability of VLPs before selecting them as candidates for vaccine or drug delivery formulations.…”