title: Ribosomal protein S19-binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism.
abstract: The hantaviral zoonotic diseases pose a significant threat to human health due to the lack of potential antiviral therapeutics or a vaccine against hantaviruses. N (Sin Nombre hantavirus nucleocapsid protein) augments mRNA translation. N binds to both the mRNA 5' cap and 40S ribosomal subunit via RPS19 (ribosomal protein S19). N with the assistance of the viral mRNA 5'-UTR preferentially favours the translation of a downstream ORF. We identified and characterized the RPS19-binding domain at the N-terminus of N. Its deletion did not influence the secondary structure, but affected the conformation of trimeric N molecules. The N variant lacking the RPS19-binding region was able to bind both the mRNA 5' cap and panhandle-like structure, formed by the termini of viral genomic RNA. In addition, the N variant formed stable trimers similar to wild-type N. Use of this variant in multiple experiments provided insights into the mechanism of ribosome loading during N-mediated translation strategy. The present study suggests that N molecules individually associated with the mRNA 5' cap and RPS19 of the 40S ribosomal subunit undergo N-N interaction to facilitate the engagement of N-associated ribosomes at the mRNA 5' cap. This has revealed new targets for therapeutic intervention of hantavirus infection.
authors: *Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
authors: Safder S
authors: SS
authors: Ganaie
authors: *Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
authors: Absarul
authors: A
authors: Haque
authors: *Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
authors: Erdong
authors: E
authors: Cheng
authors: *Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
authors: Tania S
authors: TS
authors: Bonny
authors: *Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
authors: Nilshad N
authors: NN
authors: Salim
authors: *Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
authors: Mohammad A
authors: MA
authors: Mir
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D006476:Orthohantavirus / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins / Q000502:physiology*; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019590:Nucleocapsid Proteins; D012269:Ribosomal Proteins; C040343:ribosomal protein S19