{"doi":"10.1128/jvi.02865-15","title":"Crystal Structure of the Measles Virus Nucleoprotein Core in Complex with an N-Terminal Region of Phosphoprotein","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            The enveloped negative-stranded RNA virus measles virus (MeV) is an important human pathogen. The nucleoprotein (N\n            <jats:sup>0</jats:sup>\n            ) 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 N\n            <jats:sup>0</jats:sup>\n            assembly onto the NC and the activity of the polymerase are regulated by the viral phosphoprotein (P). In this study, we pulled down an N\n            <jats:sup>0</jats:sup>\n            <jats:sub>1-408</jats:sub>\n            fragment lacking most of its C-terminal tail domain by several affinity-tagged, N-terminal P fragments to map the N\n            <jats:sup>0</jats:sup>\n            -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 N\n            <jats:sup>0</jats:sup>\n            binding peptide, P\n            <jats:sub>1-48</jats:sub>\n            , to the C terminus of an N\n            <jats:sup>0</jats:sup>\n            <jats:sub>21-408</jats:sub>\n            fragment lacking both the N-terminal peptide and the C-terminal tail of N protein to reconstitute and crystallize the N\n            <jats:sup>0</jats:sup>\n            -P complex. We solved the X-ray structure of the resulting N\n            <jats:sup>0</jats:sup>\n            -P chimeric protein at a resolution of 2.7 Å. The structure reveals the molecular details of the conserved N\n            <jats:sup>0</jats:sup>\n            -P interface and explains how P chaperones N\n            <jats:sup>0</jats:sup>\n            , preventing both self-assembly of N\n            <jats:sup>0</jats:sup>\n            and its binding to RNA. Finally, we propose a model for a preinitiation complex for RNA polymerization.\n          </jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE</jats:bold>\n            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.\n          </jats:p>","journal":"Journal of Virology","year":2016,"id":664883,"datarank":0.6628260911694899,"base_score":4.418840607796598,"endowment":4.418840607796598,"self_citation_contribution":0.6628260911694899,"citation_network_contribution":0.0,"self_endowment_contribution":0.6628260911694899,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":82,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1736150,"name":"Lassi Liljeroos","orcid":null,"position":1,"is_corresponding":false},{"id":1736152,"name":"Prasad Kasaragod","orcid":null,"position":2,"is_corresponding":false},{"id":887209,"name":"Tommi Kajander","orcid":"0000-0002-5094-227X","position":3,"is_corresponding":false},{"id":943273,"name":"Sarah J. Butcher","orcid":"0000-0001-7060-5871","position":4,"is_corresponding":false},{"id":1736149,"name":"Sergey G. Guryanov","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Crystal Structure of the Measles Virus Nucleoprotein Core in Complex with an N-Terminal Region of Phosphoprotein","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            The enveloped negative-stranded RNA virus measles virus (MeV) is an important human pathogen. The nucleoprotein (N\n            <jats:sup>0</jats:sup>\n            ) 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 N\n            <jats:sup>0</jats:sup>\n            assembly onto the NC and the activity of the polymerase are regulated by the viral phosphoprotein (P). In this study, we pulled down an N\n            <jats:sup>0</jats:sup>\n            <jats:sub>1-408</jats:sub>\n            fragment lacking most of its C-terminal tail domain by several affinity-tagged, N-terminal P fragments to map the N\n            <jats:sup>0</jats:sup>\n            -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 N\n            <jats:sup>0</jats:sup>\n            binding peptide, P\n            <jats:sub>1-48</jats:sub>\n            , to the C terminus of an N\n            <jats:sup>0</jats:sup>\n            <jats:sub>21-408</jats:sub>\n            fragment lacking both the N-terminal peptide and the C-terminal tail of N protein to reconstitute and crystallize the N\n            <jats:sup>0</jats:sup>\n            -P complex. We solved the X-ray structure of the resulting N\n            <jats:sup>0</jats:sup>\n            -P chimeric protein at a resolution of 2.7 Å. The structure reveals the molecular details of the conserved N\n            <jats:sup>0</jats:sup>\n            -P interface and explains how P chaperones N\n            <jats:sup>0</jats:sup>\n            , preventing both self-assembly of N\n            <jats:sup>0</jats:sup>\n            and its binding to RNA. Finally, we propose a model for a preinitiation complex for RNA polymerization.\n          </jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE</jats:bold>\n            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.\n          </jats:p>","is_dataset_classified":null,"base_score":4.418840607796598,"endowment":4.418840607796598,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26719278","pmcid":"PMC4810662","openalex_id":"https://openalex.org/W2199480726","authors":[],"funders":[{"funder_name":"Suomen Akatemia","grant_id":"139178","title":"Mechanisms underpinning virus interactions with host cells"},{"funder_name":"Suomen Akatemia","grant_id":"275199","title":"Nanotracking of RNA virus entry and assembly"},{"funder_name":"Sigrid Juselius Foundation","grant_id":"","title":null},{"funder_name":"Biocenter Finland","grant_id":"","title":null}],"total_grants":4,"fwci":5.1276,"citation_percentile":0.96226291,"influential_citations":0,"citation_trend":[{"year":2016,"count":10},{"year":2017,"count":6},{"year":2018,"count":9},{"year":2019,"count":11},{"year":2020,"count":12},{"year":2021,"count":11},{"year":2022,"count":11},{"year":2023,"count":2},{"year":2024,"count":3},{"year":2025,"count":3},{"year":2026,"count":4}],"oa_status":"bronze","license":"ASM Journals Non-Commercial TDM","oa_locations":[{"url":"https://jvi.asm.org/content/jvi/90/6/2849.full.pdf","host_type":"journal"},{"url":"https://jvi.asm.org/content/jvi/90/6/2849.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02865-15","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.02865-15","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26719278","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4810662","host_type":"repository"},{"url":"http://hdl.handle.net/10138/223843","host_type":"journal"},{"url":"https://dx.doi.org/10.1128/jvi.02865-15","host_type":""},{"url":"https://doi.org/10.1128/JVI.02865-15","host_type":""}],"fields_of_study":["Virology and Viral Diseases","Viral Infections and Immunology Research","Virus-based gene therapy research","0301 basic medicine","03 medical and health sciences","0303 health sciences","Centrifugation","Crystallography, X-Ray","DNA Mutational Analysis","Measles virus","Models, Molecular","Nucleocapsid Proteins","Nucleoproteins","Phosphoproteins","Protein Binding","Protein Conformation","Protein Interaction Mapping","Viral Proteins"],"mesh_terms":["Centrifugation","DNA Mutational Analysis","Measles virus","Models, Molecular","Nucleoproteins","Phosphoproteins","Protein Binding","Protein Conformation","Viral Proteins","Crystallography, X-Ray","Nucleocapsid Proteins","Protein Interaction Mapping"],"keywords":["Nucleoprotein","Phosphoprotein","Biology","Measles virus","RNA","Molecular biology","Viral protein","Polymerase","Virology","Binding site","Transcription preinitiation complex","Virus","DNA","Biochemistry","Phosphorylation","Gene","Models, Molecular","Protein Conformation","DNA Mutational Analysis","PROTEIN","Centrifugation","Crystallography, X-Ray","Viral Proteins","TEMPLATE","DOMAIN","Protein Interaction Mapping","Plant biology, microbiology, virology","RNA COMPLEX","Biochemistry, cell and molecular biology","REQUIRES","VESICULAR STOMATITIS-VIRUS","Nucleocapsid Proteins","NUCLEOCAPSIDS","Phosphoproteins","Nucleoproteins","SYSTEM","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-13T04:27:16.823915Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}