Crystal Structure of the Measles Virus Nucleoprotein Core in Complex with an N-terminal Region of Phosphoprotein

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Guryanov , S , Liljeroos , L J P , Kasaragod , P , Kajander , T A & Butcher , S J 2016 , ' Crystal Structure of the Measles Virus Nucleoprotein Core in Complex with an N-terminal Region of Phosphoprotein ' , Journal of Virology , vol. 90 , no. 6 , pp. 2849-2857 . https://doi.org/10.1128/JVI.02865-15

Title: Crystal Structure of the Measles Virus Nucleoprotein Core in Complex with an N-terminal Region of Phosphoprotein
Author: Guryanov, Sergey; Liljeroos, Lassi Juho Petteri; Kasaragod, Prasad; Kajander, Tommi Antero; Butcher, Sarah Jane
Other contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology


Date: 2016
Language: eng
Number of pages: 9
Belongs to series: Journal of Virology
ISSN: 0022-538X
DOI: https://doi.org/10.1128/JVI.02865-15
URI: http://hdl.handle.net/10138/223843
Abstract: ABSTRACT The enveloped negative-stranded RNA virus measles virus (MeV) is an important human pathogen. The nucleoprotein (N0) assembles with the viral RNA into helical ribonucleocapsids (NC) which are, in turn, coated by a helical layer of the matrix protein. The viral polymerase complex uses the NC as its template. The N0 assembly onto the NC and the activity of the polymerase are regulated by the viral phosphoprotein (P). In this study, we pulled down an N0 1-408 fragment lacking most of its C-terminal tail domain by several affinity-tagged, N-terminal P fragments to map the N0-binding region of P to the first 48 amino acids. We showed biochemically and using P mutants the importance of the hydrophobic interactions for the binding. We fused an N0 binding peptide, P1-48, to the C terminus of an N0 21-408 fragment lacking both the N-terminal peptide and the C-terminal tail of N protein to reconstitute and crystallize the N0-P complex. We solved the X-ray structure of the resulting N0-P chimeric protein at a resolution of 2.7 Å. The structure reveals the molecular details of the conserved N0-P interface and explains how P chaperones N0, preventing both self-assembly of N0 and its binding to RNA. Finally, we propose a model for a preinitiation complex for RNA polymerization. IMPORTANCE Measles virus is an important, highly contagious human pathogen. The nucleoprotein (N) binds only to viral genomic RNA and forms the helical ribonucleocapsid that serves as a template for viral replication. We address how N is regulated by another protein, the phosphoprotein (P), to prevent newly synthesized N from binding to cellular RNA. We describe the atomic model of an N-P complex and compare it to helical ribonucleocapsid. We thus provide insight into how P chaperones N and helps to start viral RNA synthesis. Our results provide a new insight into mechanisms of paramyxovirus replication. New data on the mechanisms of phosphoprotein chaperone action allows better understanding of virus genome replication and nucleocapsid assembly. We describe a conserved structural interface for the N-P interaction which could be a target for drug development to treat not only measles but also potentially other paramyxovirus diseases.
Subject: 1183 Plant biology, microbiology, virology
1182 Biochemistry, cell and molecular biology
VESICULAR STOMATITIS-VIRUS
RNA COMPLEX
PROTEIN
DOMAIN
NUCLEOCAPSIDS
POLYMERASE
TEMPLATE
REQUIRES
SYSTEM
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