9PFR

Cryo-EM structure of the respiratory syncytial virus polymerase (L:P) in NTP-bound elongation state

Summary for 9PFR

• Entry DOI: 10.2210/pdb9pfr/pdb
• EMDB information: 71611
• Descriptor: RNA-directed RNA polymerase L, Phosphoprotein, RNA (5'-R(P*AP*CP*G)-3'), ... (6 entities in total)
• Functional Keywords: respiratory syncytial virus, rna-dependent rna polymerase, nucleotide addition cycle, viral protein-rna complex, viral protein, transferase-rna complex, transferase/rna
• Biological source: Respiratory syncytial virus; More
• Total number of polymer chains: 7
• Total formula weight: 364499.08

Authors

Cao, D.,Chen, Z.,Gao, Y.,Roesler, C.,Gooneratne, I.,Liang, B. (deposition date: 2025-07-06, release date: 2026-05-06)

Primary citation

Cao, D.,Chen, Z.,Gao, Y.,Roesler, C.,Gooneratne, I.,Mera, C.,Zhuang, L.,Slack, J.,Nudell-Cook, E.,Vy, J.,Berry, J.,Royal, M.,Shaik, M.,Youngs, R.,Liang, B.
Orchestrated and dynamic nucleotide addition cycle during respiratory syncytial virus early-stage elongation.
Nat Commun, 2026

PubMed Abstract: The respiratory syncytial virus (RSV) polymerase (L:P complex) is responsible for viral RNA transcription and replication, where nucleotide addition cycles (NACs) are executed repeatedly during elongation in both processes. Using cryo-EM, we capture snapshots of RSV polymerase in action during early-stage elongation and in four distinct NAC states: NTP-bound, pre-reaction, pre-translocation, and post-translocation. Strikingly, we observe all five domains of RSV L in NTP-bound and post-translocation states. In contrast, only two domains are visible in pre-reaction and pre-translocation states, similar to previously reported apo or promoter-bound structures. Importantly, these snapshots reveal the synergistic and dynamic interaction networks among key residues and motifs of RSV polymerase, RNA template, product, incoming nucleotide, and metal ions across NAC states. Our findings provide the first comprehensive insights into orchestrated macro-domain rearrangements and micro-motif changes of RSV polymerase during NAC catalysis, facilitating antiviral therapeutics targeting RSV and related nonsegmented negative-sense RNA viruses, including rabies, Nipah, and Ebola.

PubMed: 42049741
DOI: 10.1038/s41467-026-72519-0

Experimental method

ELECTRON MICROSCOPY (3.08 Å)