Dynamic ensembles of SARS-CoV-2 N-protein reveal head-to-head coiled-coil-driven oligomerization and phase separation.

ABSTRACT: The SARS-CoV-2 nucleocapsid (N) protein is essential for the viral life cycle, facilitating RNA packaging, replication, and host-cell interactions. Its ability to self-assemble and undergo phase separation is critical for these functions but remains poorly understood. Using an integrated approach combining small-angle X-ray scattering (SAXS), nuclear magnetic resonance spectroscopy, computational modeling, and biophysical assays, we uncover key mechanisms underpinning N-protein's dynamic self-assembly. We show that the N-protein's interdomain linker (IDL) contains a conserved coiled-coil (CC) motif that drives transient interactions between protein subunits, enabling the formation of progressively larger complexes at higher concentrations. SAXS analysis and ensemble modeling reveal that th

SUBMITTER: Hernandez G 

PROVIDER: S-EPMC12159747 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature