Solution Structure of Nucleoprotein Domain 1 from the Emerging Yezo Virus

Area of Science:

• Virology
• Structural Biology
• Biochemistry

Background:

• Yezo virus (YEZV) is an emerging tick-borne orthonairovirus causing human febrile illness.
• Viral nucleoproteins (N) are crucial for YEZV replication and immune evasion.
• Lack of structural data for YEZV proteins impedes therapeutic development.

Purpose of the Study:

• To determine the first solution structure of the Yezo virus nucleoprotein domain 1 (YEZV N D1).
• To provide insights into YEZV molecular architecture and pathogenesis.

Main Methods:

• Production of a soluble, tag-free recombinant YEZV N D1.
• Integrated structural analysis using size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS).
• Computational modeling with AlphaFold 3 and all-atom molecular dynamics simulations.

Main Results:

• The YEZV N D1 adopts a stable, predominantly α-helical globular fold.
• The protein remains monomeric under near-physiological conditions.
• Experimental SEC-SAXS data strongly correlate with computational models, indicating moderate flexibility.

Conclusions:

• The determined YEZV N D1 structure offers critical insights into viral molecular architecture.
• This structural information is foundational for developing YEZV serological assays and structure-guided therapeutics.
• The findings support countermeasure development for YEZV and related emerging orthonairoviruses.