An international collaboration of scientists has revealed the molecular function of a protein essential for replication of H5N1 influenza virus. A subdomain of the viral polymerase undergoes large-scale structural reorganisation to enable an essential part of the polymerase to enter the nucleus of the infected cell, where the viral genome is replicated.
The study, published in the Journal of the American Chemical Society, illustrates how the flexibility of a protein allows it to adapt its function, facilitating infection of the host.
The polymerase allows the virus to reproduce copies of its genomic material in the infected cell, and thereby produce new viruses. It is known that adaptation of the influenza virus occurs through mutations in the viral polymerase, in particular in the C-terminal domain 627-NLS of the PB2 polymerase protein. This two-domain protein is required for import of the viral polymerase into the nucleus, by binding to importin-alpha
Researchers were able to show for the first time, using nuclear magnetic resonance spectroscopy (NMR), small angle scattering (SAS) and single molecule Förster resonance energy transfer (FRET), that in solution the protein exhibits a far more complex behaviour. In fact the conformation described by crystal structure exists in solution. They were also able to show that this 'open' form of the protein interacts with importin-alpha and it is this conformational equilibrium that allows for PB2 to enter the nucleus.
http://pubs.acs.org/doi/10.1021/jacs.5b07765