NP - central disordered linker

(Carlson MolCell 2020 PMID: 33248025) The central disordered linker contains a conserved serinearginine (SR)-rich sequence that is likely to serve as a key regulatory hub in N protein function. Early in infection, the SR region is rapidly phosphorylated at multiple sites by cytoplasmic kinases (Bouhaddou et al., 2020; Davidson et al., 2020; Fung and Liu, 2018; Klann et al., 2020; Peng et al., 2008; Stohlman et al., 1983; Surjit et al., 2005; White et al., 2007; Wu et al., 2014; Wu et al., 2009). Phosphorylation leads to association with the RNA helicase DDX1, which promotes RNA structural changes required for transcription of long subgenomic RNAs in the RTC (Wu et al., 2014). Later in infection, nucleocapsid formation and viral assembly do not seem to require N protein phosphorylation, which is substantially reduced in the nucleocapsid of MHV and SARS-CoV virions (Wu et al., 2014; Wu et al., 2009). We have little understanding of the molecular mechanisms by which phosphorylation influences N protein function.

The ordered, gellike condensates of the unmodified protein are changed to more liquid-like droplets by phosphorylation, providing a potential structural foundation for the distinct functions of the N protein in nucleocapsid assembly and genome processing.

pmid: 33479198 /2021

central disordered domain drives phase separation with RNA, and that phosphorylation of an adjacent serine/arginine rich region modulates the physical properties of the resulting condensates.

The SARS-CoV-2 membrane (M) protein independently induces N protein phase separation, and three-component mixtures of N + M + RNA form condensates with mutually exclusive compartments containing N + M or N + RNA, including annular structures in which the M protein coats the outside of an N + RNA condensate.