The cryoEM structure of the Hendra henipavirus nucleoprotein reveals insights into paramyxoviral nucleocapsid architectures

• Published in: Scientific reports Vol. 14; no. 1; pp. 14099 - 20
• Main Authors: Passchier, Tim C, White, Joshua B. R, Maskell, Daniel P, Byrne, Matthew J, Ranson, Neil A, Edwards, Thomas A, Barr, John N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 18.06.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: Electrostatic properties; Hydrophobicity; Molecular biology; N protein; N-Terminus; Nucleocapsids; Nucleotides; Protein folding; Proteins; Ribonucleic acid; RNA
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-58243-z

We report the first cryoEM structure of the Hendra henipavirus nucleoprotein in complex with RNA, at 3.5 Å resolution, derived from single particle analysis of a double homotetradecameric RNA-bound N protein ring assembly exhibiting D14 symmetry. The structure of the HeV N protein adopts the common bi-lobed paramyxoviral N protein fold; the N-terminal and C-terminal globular domains are bisected by an RNA binding cleft containing six RNA nucleotides and are flanked by the N-terminal and C-terminal arms, respectively. In common with other paramyxoviral nucleocapsids, the lateral interface between adjacent Ni and Ni+1 protomers involves electrostatic and hydrophobic interactions mediated primarily through the N-terminal arm and globular domains with minor contribution from the C-terminal arm. However, the HeV N multimeric assembly uniquely identifies an additional protomer-protomer contact between the Ni+1 N-terminus and Ni−1 C-terminal arm linker. The model presented here broadens the understanding of RNA-bound paramyxoviral nucleocapsid architectures and provides a platform for further insight into the molecular biology of HeV, as well as the development of antiviral interventions.