Group of prof. Konstantin Severinov just won a grant from prestigious joint Royal Society (UK) – Russian Foundation for Basic Research program. Projects for such programs undergo double-selection (by each partner) and thus are more difficult to be supported with funding.
Supported project is focused on understanding the mechanism by which empty capsids (the protein shell of a virus) are filled with genomic DNA during virus particle assembly. In most viruses that replicate within a bacterium (also called bacteriophages), as well as in evolutionarily related animal viruses (e.g. herpes), this task is performed by a specialized nanomotor that uses energy released during ATP hydrolysis, for packaging viral DNA into the capsid. These DNA packaging nanomotors are the most powerful molecular machines discovered in nature so far. They can generate forces reaching ~50 pN, translocating genomic DNA into empty capsids with the speed of ~100 base pairs per second, and packaging DNA to a crystalline density. Unsurprisingly, these nanomotors could be exploited in novel biotechnological processes requiring controlled transfer of nucleic acids across barriers (e.g. DNA sequencing and gene therapy) benefitting the wider population from improved therapeutic approaches and reduced healthcare costs.
To inform future research, we first need to understand how the nanomotor works. Our colleagues from the University of York have a track record in studying these motors. However, despite progress, their studies have been limited by the relatively unstable nature of the bacteriophage proteins they have had available to study. This project represents an exciting new opportunity, as we will be able to start new collaboration on studying motors present in thermostable bacteriophages, which have been collected and purified by members of our laboratory in Moscow. We will study target proteins selected for their enhanced stability because it makes the process of determining their three-dimensional molecular structure quicker and more straightforward. They are also often best suited for preparation of stable complexes with other proteins, for biochemical and structural studies. We aim to reconstruct under laboratory conditions the process of DNA translocation into empty capsids, by adding motor protein and DNA to the empty capsid particles. We will use X-ray crystallography to study the structure of individual proteins and Electron Microscopy (EM) for studying the structure of larger DNA translocating assemblies.
In general, this collaborative research offers the York and Moscow labs to commence a Cryo-EM mediated research program, providing new possibilities for larger-scale collaborative research with impact in biotechnology, and training opportunities for junior researchers.