Biochemie der Signaldynamik

Eine deutsche Beschreibung unserer Forschung wird in Kürze verfügbar sein.


Figure 1: Horma domains provide an alternative mechanism to create a dynamic spatio-temporal controlled signal transduction.

Spatiotemporal control of protein interactions in signaling pathways is vital in biology. The reversible activation of signaling proteins or complexes through post-translational modifications (PTMs) plays a central role in the regulation of biochemical switches in signal-transducing systems (Figure 1a). The primary interest of our research group is in a less studied alternative process in cellular signaling, which is operational in cell division, DNA damage signaling, and autophagy. The signal transduction mechanism relies on the reversible change of a protein’s three-dimensional structure to regulate its protein-protein interaction potential. Central to this process is the extraordinary ability of HORMA (HOP1, REV7, MAD2) domains to wrap their C-terminal tail around an interacting peptide motif, thereby creating a very stable but temporary signaling complex (Figure 1b). The crucial paradigm emerging from our previous studies in cell division is that structural conversion of HORMA domains is catalyzed, both at the assembly and the disassembly level, by specialized protein machinery, allowing dynamic control of signaling. We are interested in the molecular mechanisms that regulate the topological changes in these signaling protein complexes, which are essential in the initiation of signaling.

Instead of studying these processes in their complex cellular environment, we aim to biochemically reconstitute these dynamic reactions from purified components in vitro. This allows us to study and manipulate all biochemical activities in great detail, identify the minimal set of components, and ultimately reveal the underlying fundamental principles. Typically, our projects use a bottom-up approach, where we build macromolecular machines from scratch to understand them in details using a combination of biochemical reconstitution, structural biology, and biophysical investigations.

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