Structural insights into phosphoprotein chaperoning of nucleoprotein in measles virus

Sergey Guryanov, Lassi Juho Petteri Liljeroos, Prasad Kasaragod, Tommi Antero Kajander, Sarah Jane Butcher

Forskningsoutput: KonferensbidragPoster

Sammanfattning

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. Here, we pulled down an N01-408 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 N021-408 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 2.7 Å resolution. 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. We compare the structure of an N0-P complex to atomic model of helical ribonucleocapsid. We thus propose a model how P may help 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 the 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 not only to treat measles but also potentially other paramyxovirus diseases.
Originalspråkengelska
Sidor46
Antal sidor1
StatusPublicerad - 2017
MoE-publikationstypEj behörig
EvenemangInstruct Biennial Structural Biology Conference 2017
- International Best Western Hotel, Brno, Tjeckien
Varaktighet: 24 maj 201726 maj 2017
https://www.structuralbiology.eu/biennial2017

Konferens

KonferensInstruct Biennial Structural Biology Conference 2017
Förkortad titelIBSBM2017
LandTjeckien
OrtBrno
Period24/05/201726/05/2017
Internetadress

Bibliografisk information

Instruct Biennial Structural Biology Conference Abstract Booklet

Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi

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