New DFG project at IBC

August 18, 2014 /

Glutamine Methylation in Proteins

Approval of a new research project with the title "Specificity and novel substrates of human protein glutamine methyltransferases". The modification of proteins plays a key role in biology. The methylation of glutamine is a rare modification that is not studied very intensively. Currently, only three glutamine methylations are known in the human proteome. These modifications are introduced by three known human glutamine methyltransferases, the cytosolic HemK2, the mitochondrial HMPrmC and the Fibrillarin enzymes. Deletion of HemK2 is lethal in mice, indicating a very important physiological role of this enzyme. It is one main goal of this work to identify additional substrates of HemK2 which may explain the lethal knock-out phenotype. One approach to reach this goal is to determine the substrate sequence specificities of the enzyme. Based on these data, we will identify novel substrate candidates and investigate their methylation in vitro and in vivo. We have already demonstrated that this approach has a great potential for discovery of novel substrates of protein methyltransferases and initial data indicate the presence of many novel peptide substrates of HemK2 and confirmed methylation at protein level in several cases and in human cells. Our results will shed light on the mechanism of substrate recognition of protein glutamine methyltransferases and the identification of novel glutamine methyltransferase targets will greatly advance our knowledge of this rare and not well studied type of post-translational modification.

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