8PDP

10-mer ring of HMPV N-RNA bound to the C-terminal region of P

Summary for 8PDP

• Entry DOI: 10.2210/pdb8pdp/pdb
• EMDB information: 17617
• Descriptor: Nucleoprotein, Phosphoprotein, RNA (3 entities in total)
• Functional Keywords: nucleoprotein, virus, nucleocapsid, rna-binding, hmpv, pneumoviridae, mononegavirales, viral protein
• Biological source: Human metapneumovirus (strain CAN97-83) (HMPV); More
• Total number of polymer chains: 3
• Total formula weight: 46562.91

Authors

Whitehead, J.D.,Decool, H.,Leyrat, C.,Carrique, L.,Fix, J.,Eleouet, J.F.,Galloux, M.,Renner, M. (deposition date: 2023-06-12, release date: 2023-12-06, Last modification date: 2024-03-20)

Primary citation

Whitehead, J.D.,Decool, H.,Leyrat, C.,Carrique, L.,Fix, J.,Eleouet, J.F.,Galloux, M.,Renner, M.
Structure of the N-RNA/P interface indicates mode of L/P recruitment to the nucleocapsid of human metapneumovirus.
Nat Commun, 14:7627-7627, 2023

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 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.

PubMed: 37993464
DOI: 10.1038/s41467-023-43434-5

Experimental method

ELECTRON MICROSCOPY (2.9 Å)