+Search query
-Structure paper
Title | Structure of the N-RNA/P interface indicates mode of L/P recruitment to the nucleocapsid of human metapneumovirus. |
---|---|
Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 7627, Year 2023 |
Publish date | Nov 22, 2023 |
Authors | Jack D Whitehead / Hortense Decool / Cédric Leyrat / Loic Carrique / Jenna Fix / Jean-François Eléouët / Marie Galloux / Max Renner / |
PubMed Abstract | Human metapneumovirus (HMPV) is a major cause of respiratory illness in young children. The HMPV polymerase (L) binds an obligate cofactor, the phosphoprotein (P). During replication and ...Human metapneumovirus (HMPV) is a major cause of respiratory illness in young children. The HMPV polymerase (L) binds an obligate cofactor, the phosphoprotein (P). During replication and transcription, the L/P complex traverses the viral RNA genome, which is encapsidated within nucleoproteins (N). An essential interaction between N and a C-terminal region of P tethers the L/P polymerase to the template. This N-P interaction is also involved in the formation of cytoplasmic viral factories in infected cells, called inclusion bodies. To define how the polymerase component P recognizes N-encapsidated RNA (N-RNA) we employed cryogenic electron microscopy (cryo-EM) and molecular dynamics simulations, coupled to activity assays and imaging of inclusion bodies in cells. We report a 2.9 Å resolution structure of a triple-complex between multimeric N, bound to both RNA and the C-terminal region of P. Furthermore, we also present cryo-EM structures of assembled N in different oligomeric states, highlighting the plasticity of N. Combined with our functional assays, these structural data delineate in molecular detail how P attaches to N-RNA whilst retaining substantial conformational dynamics. Moreover, the N-RNA-P triple complex structure provides a molecular blueprint for the design of therapeutics to potentially disrupt the attachment of L/P to its template. |
External links | Nat Commun / PubMed:37993464 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.9 - 4.7 Å |
Structure data | EMDB-17613, PDB-8pdl: EMDB-17614, PDB-8pdm: EMDB-17615, PDB-8pdn: EMDB-17616, PDB-8pdo: EMDB-17617, PDB-8pdp: EMDB-17618, PDB-8pdq: EMDB-17619, PDB-8pdr: EMDB-17620, PDB-8pds: |
Source |
|
Keywords | VIRAL PROTEIN / Nucleoprotein / Virus / Nucleocapsid / RNA-binding / HMPV / Pneumoviridae / Mononegavirales |