In the Heinemann laboratory, crystallographic analysis is combined with biochemical and biophysical experiments to elucidate the molecular basis of central intracellular processes at atomic detail. One strand of research addresses the regulation of gene expression at the levels of transcription initiation or mRNA homeostasis. The transcription factor Klf4 is involved in controlling the differentiation state of cells and has been used in a cocktail with three other transcription factors to re-program terminally differentiated cells to a state of pluripotency. The crystal structure of the DNA-binding domain of Klf4 bound to its cognate DNA sequence reveals the structural basis of DNA sequence recognition by this protein. Proteins regulating the fate of mRNA in cells are often composed of RNA-binding modules.
One such module is the cold shock domain which we study in bacterial cold shock proteins and mammalian factors such as YB-1 or Lin28. It has been demonstrated that cold shock domains bind extended DNA or RNA single strands with pyrimidine-preferential contacts at a conserved protein surface with seven distinct sub-sites.
A second strand of research uses the same methodology to investigate aspects of intracellular transport. In collaboration with the Sommer and Wanker laboratories, factors involved in ER-associated protein degradation and protein retro-translocation from the ER into the cytoplasm are studied. We are also interested in the structural basis of intracellular transport, in particular the tethering of ER-derived vesicles to the Golgi membrane. Within the Helmholtz Protein Sample Production Facility we produce proteins, crystals and crystal structure for collaborating laboratories.
Our work is greatly facilitated by privileged access to the synchrotron storage ring BESSY in Berlin.