Structural biologists in the lab of IMP senior scientist Tim Clausen have characterised the structure of the protein arginine kinase McsB, a novel class of regulatory enzymes. Their findings, which are reported in "Nature Chemical Biology", hint at a complex signalling system operating in bacteria.
"Quis custodiet ipsos custodes?" ("Who watches the watchmen?"), asks a Latin phrase. It’s a valid question in biology, too. Most cellular processes are controlled by proteins, but what controls proteins themselves? This task is in part performed by a specialised class of proteins known as protein kinases, which attach a small chemical unit called phosphoryl group to other proteins. This process is called “phosphorylation” and changes the activity or lifetime of its targets. The discovery of protein phosphorylation as a key regulatory mechanism in the 1950s was awarded a Nobel prize in 1992.
Most known protein kinases found in organisms from bacteria to humans are similar to each other and stem from the same ancestral gene. Scientists from the lab of Tim Clausen at the Research Institute of Molecular Pathology (IMP) in Vienna now unravelled the atomic structure of the novel protein kinase McsB that is found in gram-positive bacteria and differs from all other protein kinases in structure and function. As such and owing to the critical role of McsB for bacterial infection, the reported findings may aid developing novel antibiotics, as reported in the journal “Nature Chemical Biology”.
What is special about McsB is that, whereas other protein kinases modify the amino acids serine, threonine, and tyrosine, McsB acts specifically on the amino acid arginine, changing it to phosphoarginine. This seemingly small difference results in completely novel regulatory mechanisms. Most importantly, phosphoarginine residues can be recognised by specific protein domains, three of which have been discovered by the Clausen lab. One of the phosphoarginine reader domains is found in ClpCP, a protein “shredder”, which results in proteins marked by McsB being quickly eliminated from the cell. This mechanism has been nicknamed “the phospho-kiss of death”, with the details of the kissing reaction now being resolved at atomic resolution.
Moreover, the scientists highlight that the distinct phosphoarginine-reader domains point to a remarkably complex signalling system – which challenges simpler views of bacterial protein phosphorylation that were suggested by previous studies.
Suskiewicz, M. et al. (2018): Structure of McsB, a protein kinase for regulated arginine phosphorylation. Nature Chemical Biology, DOI: http://dx.doi.org/10.1038/s41589-019-0265-y
About the IMP
The Research Institute of Molecular Pathology (IMP) in Vienna pursues world-class research in basic molecular biology. It is located at the Vienna BioCenter and largely sponsored by Boehringer Ingelheim. With over 200 scientists from 40 countries, the IMP is committed to scientific discovery of fundamental molecular and cellular mechanisms underlying complex biological phenomena. www.imp.ac.at
About the Vienna BioCenter
The Vienna BioCenter is a leading life sciences hub in Europe, offering an extraordinary combination of research, business and education in a single location. Over 1,800 employees, 90 research groups, 24 biotech companies, 1,300 students and scientists from 70 countries create a highly dynamic and stimulating environment. www.viennabiocenter.org