Structural Insights into the Stability of the Human STAT1–Nipah Virus V Protein Complex from Molecular Dynamics Simulations
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Abstract
Background: Nipah virus (NiV) phosphoprotein gene encodes multiple non-structural accessory proteins, including W, V, and C, which antagonise host innate antiviral defences by inhibiting interferon (IFN) signalling through suppression of interferon-stimulated genes (ISGs). The V protein has been reported to target host signal transducers and activators of transcription (STAT), particularly STAT1, by forming a high-molecular-weight STAT1/V assembly. However, the structural and dynamic behaviour of these assemblies remains poorly understood.
Methods: In this study, we employed molecular docking and molecular dynamics (MD) simulations to compare the structural behaviour of apo-STAT1 with that of the STAT1/V complex. The NiV V peptide structure was first predicted using an ab initio Rosetta modelling approach before complex generation.
Results: Computational modelling predicted a locally ordered core within the NiV V peptide (114–140). HADDOCK docking identified a dominant cluster (score −64.6 ± 11.2; Z-score −2.2) with strong electrostatic contributions and a 1278.7 Å2 buried surface area. MD analyses revealed that V binding enhances STAT1 structural stability and reduces conformational flexibility throughout the simulations.
Conclusion: Collectively, these findings provide computational support for in vitro observations of stable STAT1/V assemblies and offer mechanistic insights into how NiV V binding interferes with IFN-β-induced STAT1 phosphorylation via the Src Homology 2 (SH2) domain.
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