Aktiviteetteja vuodessa
Abstrakti
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.
Alkuperäiskieli | englanti |
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Sivut | 46 |
Sivumäärä | 1 |
Tila | Julkaistu - 2017 |
OKM-julkaisutyyppi | Ei sovellu |
Tapahtuma | Instruct Biennial Structural Biology Conference 2017 - International Best Western Hotel, Brno, Tšekki Kesto: 24 toukok. 2017 → 26 toukok. 2017 https://www.structuralbiology.eu/biennial2017 |
Konferenssi
Konferenssi | Instruct Biennial Structural Biology Conference 2017 |
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Lyhennettä | IBSBM2017 |
Maa/Alue | Tšekki |
Kaupunki | Brno |
Ajanjakso | 24/05/2017 → 26/05/2017 |
www-osoite |
Lisätietoja
Instruct Biennial Structural Biology Conference Abstract BookletTieteenalat
- 1182 Biokemia, solu- ja molekyylibiologia
Laitteet
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Instruct-HiLIFE CryoEM core facility
Sarah Butcher (Johtaja), Ausra Domanska (Operaattori), Pasi Laurinmäki (Operaattori) & Benita Löflund (Operaattori)
Biotekniikan instituuttiLaitteistot/tilat: Keskuspalveluyksikkö
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INSTRUCT HILIFE protein crystallography platform
Tommi Kajander (Johtaja)
Biotekniikan instituuttiLaitteistot/tilat: Keskuspalveluyksikkö
Aktiviteetit
- 1 Konferensseihin, kursseille ja seminaareihin osallistuminen ja näiden järjestäminen
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Instruct Biennial Structural Biology Conference 2017
Sergei Gurianov (Posteriesitys)
24 toukok. 2017 → 26 toukok. 2017Aktiviteetti: Tapahtumaan osallistumisen ja tapahtuman järjestämisen tyypit › Konferensseihin, kursseille ja seminaareihin osallistuminen ja näiden järjestäminen
Tiedosto