Summary information and primary citation
- PDB-id
-
7nkr;
DSSR-derived features in text and
JSON formats
- Class
- viral protein
- Method
- cryo-EM (5.6 Å)
- Summary
- 1918 h1n1 viral influenza polymerase heterotrimer with
nb8210
- Reference
-
Keown JR, Zhu Z, Carrique L, Fan H, Walker AP, Serna
Martin I, Pardon E, Steyaert J, Fodor E, Grimes JM
(2022): "Mapping
inhibitory sites on the RNA polymerase of the 1918
pandemic influenza virus using nanobodies." Nat
Commun, 13, 251. doi: 10.1038/s41467-021-27950-w.
- Abstract
- Influenza A viruses cause seasonal epidemics and global
pandemics, representing a considerable burden to healthcare
systems. Central to the replication cycle of influenza
viruses is the viral RNA-dependent RNA polymerase which
transcribes and replicates the viral RNA genome. The
polymerase undergoes conformational rearrangements and
interacts with viral and host proteins to perform these
functions. Here we determine the structure of the 1918
influenza virus polymerase in transcriptase and replicase
conformations using cryo-electron microscopy (cryo-EM). We
then structurally and functionally characterise the binding
of single-domain nanobodies to the polymerase of the 1918
pandemic influenza virus. Combining these functional and
structural data we identify five sites on the polymerase
which are sensitive to inhibition by nanobodies. We propose
that the binding of nanobodies at these sites either
prevents the polymerase from assuming particular functional
conformations or interactions with viral or host factors.
The polymerase is highly conserved across the influenza A
subtypes, suggesting these sites as effective targets for
potential influenza antiviral development.
