CRC 1093 - Project Area B
Area B: Biological Targets
Project Area B represents the biologically oriented groups, who each provide one or more protein targets. Here biological questions will be answered by supramolecular chemistry.
Protein complexity increases from B4 and B5 (dimeric proteins) to B1, B2, B6 and B7 (protein machines): B1 (Ehrmann) uses tailored supramolecular ligands to modulate the assembly and function of HtrA proteases and will develop new strategies for the repair of pathogenic protein conformations; B2 (Meyer) similarly applies supramolecular chemistry combined with newly developed biochemical approaches to clarify how the Cdc48/p97 segregase works on the molecular level. The focus lies on three prominent structural elements: the central pore, the adapter binding site and the p97 surface of the N domain. Modulation of 14-3-3 protein-protein interactions is accomplished in B4 (Ottmann), with a dual emphasis on supramolecular inhibition and activation. B5 (Knauer) and B6 (Musacchio) both involve Survivin, with B5 focusing on the development of export signal inhibitors. Moreover B5 targets the nuclear import signal of the protease Taspase1. B6 characterizes supramolecular compounds that interfere with, or modulate, the localization of the Chromosomal Passenger Complex (CPC) to the centromere in mitosis. A recently established assay for the in vitro biochemical reconstitution of kinetochores will allow to test the potential of these compounds to modulate reversible protein-protein interactions. Under a slightly different focus B7 (Westermann) examines the functional coupling between kinetochores and microtubuli. To address this largely unexplored field, supramolecular chemistry will be employed to reconstitute multivalent kinetochore-microtubule attachments in vitro and specifically perturb their function using tailored chemical compounds in combination with DNA origami architectures from A6.