Back

Pressure-cooling remodeling of TMV coat protein reveals mechanically partitioned capsid dynamics and selective epitope masking

Bonafe, C. F. S.; Teixeira, J. P.; Freire, C. C. d. M.; Bajay, M. M.; de Lima Neto, D. F.

2026-06-01 microbiology
10.64898/2026.05.31.729108 bioRxiv
Show abstract

High hydrostatic pressure (HHP) perturbs protein assemblies by shifting conformational equilibria toward lower-volume states and by reorganizing hydration at cavities, interfaces, and solvent-exposed surfaces (Heremans 1982; Akasaka 2006; Roche et al. 2012; Hata, Nishiyama, and Kitao 2020). Here, we integrate pressure-dependent molecular dynamics descriptors, pressure-temperature interpretation, structure-based epitope prediction, and face-resolved intersubunit metrics to examine how pressure and pressure-cooling treatment remodel the tobacco mosaic virus coat protein (TMVcp) assembly. The pressure response is not adequately explained as uniform shrinkage. Instead, the data support a hierarchical transition from a broad, native-like conformational ensemble at low pressure, through a cooperative compacting regime around 1000- 1750 bar, toward a high-pressure compact state with reduced configurational diversity, suppressed global mobility, and localized residual fragility. A representative TMVcp face composed of A2, A3, A4, A19, A20, A21, A35, A36, and A37 behaves as a mechanically partitioned network: A3 behaves as a principal deformation hub, A20-A21-A35-A37 forms a lateral/diagonal compression corridor, A21 behaves as a bridge node, A36 acts as an anisotropic relay, and A2, A4, and A19 behave as stabilizing or adaptive anchors. Pairwise minimum-distance profiles, per-subunit radius of gyration, and post-fit RMSD converge around a late trajectory interval near 358-365 ns, suggesting a coordinated face-level breathing event rather than independent stochastic noise. These local dynamics provide a conservative structural explanation for predicted pressure-dependent epitope remodeling: HHP may mask canonical solvent-exposed epitopes by reducing loop mobility and closing intersubunit grooves, whereas pressure followed by low-temperature trapping may selectively preserve only protrusions compatible with the compact, hydration-trapped lattice. Because DiscoTope and ElliPro are computational predictors, these results should be interpreted as structural hypotheses requiring experimental validation by antibody binding assays, mutagenesis, HDX-MS, or high-pressure structural approaches.

Matching journals

The top 2 journals account for 50% of the predicted probability mass.