X-ray crystallographic studies of the SMN-complex
Before genetic information can be translated into proteins non-coding regions, the so called introns, have to be removed from the pre-messenger RNA. The latter is the primary transcript of genetic information contained on the chromosome. Within the eukaryotic cell, this task is facilitated by a huge and complex machinery, the spliceosome. It is not surprising that the assembly of such a complex machine affords, in turn, another complicated machinery. Our research focus is on this molecular assembly machine, the SMN complex. The SMN complex coordinates the formation of basic spliceosomal building blocks called snRNPs. At the heart of this complex is the name-giving survival motor neuron (SMN) protein. Mutations within the gene coding for SMN have been identified as the cause for spinal muscular atrophy (SMA).
We have solved the crystal structures of two key intermediates of the assisted snRNP assembly process. Based on the two protein structures we propose a mechanism how snRNPs are assembled in the crowded environment of the eukaryotic cytoplasm. Read more ...
Structural Biology of LARPs
Several La-related proteins (LARPs) seem to play an important role in the regulation of the process of translation of messenger RNA into proteins. To understand the molecular details of these regulatory processes, we are currently crystallizing different RNA/protein and protein/peptide complexes.
Growing crystals of suitable size and quality is -obviously- the first and most important step of every structure determination project. The ability to increase the success rate during initial crystallization screening as well as crystal optimization will have a significant impact on the overall success rate. Amongst other strategies, we have recently focused on the use of alternative polymeric precipitants to overcome possible limits of the popular polyethylene glycols (PEGs). A commercial screen that exploits the chemical diversity of water soluble polymers as a variable of the 'crystallization space' is marketed as a collaboration with Molecular Dimensions Ltd.