Intrinsic disorder in measles virus nucleocapsids

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Measles virus nucleoprotein (N) forms helical nucleocapsids essential for viral RNA packaging.
• The intrinsically disordered C-terminal domain (N(TAIL)) of N interacts with phosphoprotein P, crucial for viral transcription and replication.
• The location of N(TAIL)'s molecular recognition element (MoRE) raises questions about its function within the nucleocapsid structure.

Purpose of the Study:

• To structurally characterize the N(TAIL) domain in situ within the intact measles virus nucleocapsid.
• To elucidate the functional role of the flexible N(TAIL) chain in viral transcription and replication.

Main Methods:

• Nuclear magnetic resonance (NMR) spectroscopy
• Small-angle scattering (SAS)
• Electron microscopy (EM)

Main Results:

• N(TAIL) exhibits high flexibility within intact nucleocapsids.
• The MoRE of N(TAIL) transiently interacts with the folded RNA-binding domain (N(CORE)).
• A model proposes N(TAIL) escapes the nucleocapsid, positioning the MoRE for polymerase complex interaction.

Conclusions:

• The study provides the first in situ structural insights into measles virus N(TAIL).
• A conformational restriction model explains N(TAIL)'s flexibility and its role in initiating viral RNA synthesis.
• This structural framework aids understanding of measles virus replication mechanisms.