The Nucleoprotein and Phosphoprotein of Measles Virus

Abstract

Measles virus is a negative strand virus and the genomic and antigenomic RNA binds to the nucleoprotein (N), assembling into a helical nucleocapsid. The polymerase complex comprises two proteins, the Large protein (L), that both polymerizes RNA and caps the mRNA, and the phosphoprotein (P) that co-localizes with L on the nucleocapsid. This review presents recent results about N and P, in particular concerning their intrinsically disordered domains. N is a protein of 525 residues with a 120 amino acid disordered C-terminal domain, N tail . The first 50 residues of N tail extricate the disordered chain from the nucleocapsid, thereby loosening the otherwise rigid structure, and the C-terminus contains a linear motif that binds P. Recent results show how the 5′ end of the viral RNA binds to N within the nucleocapsid and also show that the bases at the 3′ end of the RNA are rather accessible to the viral polymerase. P is a tetramer and most of the protein is disordered; comprising 507 residues of which around 380 are disordered. The first 37 residues of P bind N, chaperoning against non-specific interaction with cellular RNA, while a second interaction site, around residue 200 also binds N. In addition, there is another interaction between C-terminal domain of P (XD) and N tail . These results allow us to propose a new model of how the polymerase binds to the nucleocapsid and suggests a mechanism for initiation of transcription.

Structural insights into RNA polymerases of negative-sense RNA viruses

“…The RNA polymerase cofactor P protein consists of three domains: an N-terminal domain (NTD), a central oligomerization domain (OD) and a C-terminal X domain (XD) 18 (Fig. 1c ).…”

“…These include the phosphoprotein (P protein) in paramyxoviruses, pneumoviruses and rhabdoviruses, M2-1 in pneumoviruses and VP24, VP30 and VP35 in filoviruses [12][13][14][15][16] . These cofactors have been implicated in tethering the polymerase to the nucleoprotein-coated RNA template and assisting in nucleoprotein recruitment to nascent RNA by forming nucleoprotein-P protein complexes to prevent premature oligomerization of nucleoprotein and nonspecific binding of nucleoprotein to RNA [17][18][19] .…”

Evolutionary history of cotranscriptional editing in the paramyxoviral phosphoprotein gene

“…The viral single-stranded RNA genome is bound to the nucleocapsid protein, forming a helical protein–nucleic acid complex which encapsulates and protects the genome ( Whelan, Barr, and Wertz 2004 ; Fearns and Plemper 2017 ; Guseva et al 2019 ). The nucleocapsid acts as a template for all virally directed RNA-synthesis.…”

“…there is no effective difference between a V protein resulting from a G 1 insertion and a V protein resulting from a G 4 insertion). This is because the mRNA flanking the edit site encodes an intrinsically disordered region of P/V/W ( Habchi and Longhi 2012 ; Longhi et al 2017 ; Guseva et al 2019 ). Any extended sequence of G nucleotides is translated into polyglycine, and while the conformational preferences of polyglycine are still not entirely established ( Ohnishi et al 2006 ; Tran, Mao, and Pappu 2008 ), the homo-polymeric sequence will be disordered.…”

Structure, dynamics and phase separation of measles virus RNA replication machinery

“…The 5' and 3' binding sites were unambiguously identified (figure 2), and thereby the register of binding of viral genomic RNA within the assembled NCLPs. This implies that the final three nucleotides at the 3' end of the genome are almost fully exposed in assembled nucleocapsids (figure 2), allowing access to the genome for the RNA-dependent RNA polymerase complex [28]. Putative protein-nucleobase interactions were identified in the RNA-binding groove (figure 2).…”