In order to be able to develop new drugs against infectious diseases, researchers need to understand their molecular basis. How does the proliferation of a pathogen proceed, what interactions take place between it and the host cell and how are these processes regulated? For this purpose, protein-RNA complexes are examined. They play an important role at different times in the lifecycle of the pathogen or the host cell and are thus involved in infection processes. Together with colleagues, Prof. Alexandre Bonvin has now developed an integrated structure analysis platform that is able to very simply and effectively calculate the structure of large protein-RNA complexes on the basis of diverse experimental data. The so-called “M3 Framework”, which is an extension of the HADDOCK software developed in the Bonvin lab, is available free of charge for non-profit researchers. The researchers published their results in the scientific journal Nature Methods.
Example of a complex protein structure calculated with the M3 Framework: the box C/D enzyme for RNA methylation.
Like tiny machines, proteins in our body do hard work. Virtually all processes are performed or controlled by these highly specialised protein molecules. They transmit signals, convert energy, initiate chemical reactions or provide growth and movement. These partially very complex protein machines, such as RNA polymerases, are not easy to decode in their structure and function. Usually, scientists use methods of protein crystallography or electron microscopy for this purpose. However, these methods can have the disadvantage that they can impair the natural form and function of the proteins and nucleic acids.
In the current project, researchers follow a different approach, studying large protein-RNA complexes in solution with nuclear magnetic resonance spectroscopy (NMR). This is a method for examining the electronic environment of individual atoms and the interactions with the neighbouring atoms. “The great advantage of the method is that we can experience complex protein machines as active enzymes at work, with their natural dynamic folding and shape,” says research leader Teresa Carlomagno (Helmholtz Centre for Infection Research).