Widespread occurrence and novel functions of proteins binding Z-DNA/RNA, the left-handed helix of nucleic acids

The first crystal structure of DNA revealed a left-handed helix, named Z-DNA. Once considered an artefact, it took a long time to convince the scientific community of its biological relevance. One of the most convincing evidence was the discovery of a protein able to bind and stabilize Z-DNA and Z-RNA, granted by a small module, named Z? domain. Over the years, 4 other proteins harbouring one or more Z? domains have been identified: either vertebrate factors in defense of infections or viral proteins to avoid or hijack these same mechanisms. Common believe is that Z-DNA/RNA is mainly involved in innate immunity. However, nature tends to capitalize and a molecular structure, endowed with a specific function, is rarely exploited in a single biological process, whereby important such as innate immunity. Aim of the project is to demonstrate that a much larger number of proteins are able to interact with Z-DNA/RNA. The modular nature of these proteins (i.e. the presence of other domains with known functions) together with the reconstruction of the evolutionary history of Z? domains will shed lights on evolutionary conserved and novel functions of Z-DNA/RNA.

Members:
Matteo De Rosa (Principal investigator)
Toni Giorgino