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Cryo-EM shows molecular machine in action

17 Jan 2018
David Haselbach

Scientists use cryo-EM imaging to describe the different conformational states of a complex molecule involved in the editing of RNA in unprecedented detail. They reported their findings in the journal Cell.

If we were able to look at enzymes in action, we would be reminded of windswept landscapes with creatures struggling in the storm. Molecular machines that perform catalytic functions constantly change their shape and never stand still.

Structural biologists use a number of sophisticated tools to find out the three dimensional shape of complex molecules. However, technologies like x-ray crystallography only yield static images or at best, they provide an average impression of numerous molecules in action.

Biophysicist David Haselbach, a principal investigator at the IMP, has now been able to use cryo-EM imaging to describe in great detail the different conformational states of the maturing spliceosome, a complex molecule involved in editing of RNA. The high-resolution images have been merged into a video that allows the researchers to visualize for the first time the functionally important steps in the assembling process. This is a critical step toward understanding how the spliceosome works.

Most of the work has been performed at the Max Planck Institute for Biophysical Chemistry in Göttingen, where David Haselbach was a postdoc before he joined the IMP in 2017. His move to the IMP further boosts research based on cryo-EM, a technology that is already well established at the Vienna BioCenter. The Haselbach lab currently has an open position for a PhD student to complement the team.

Original Publication

David Haselbach, Ilya Komarov, Dmitry E. Agafonov, Klaus Hartmuth, Benjamin Graf, Olexandr Dybkov, Henning Urlaub, Berthold Kastner, Reinhard Lührmann & Holger Stark (2018).

"Structure and Conformational Dynamics of the Human Spliceosomal Bact Complex". Cell.