Exploring the origins of protein allostery
Dr Jamie Taka in the laboratory (photo supplied)
Allostery is a fundamental regulatory mechanism underpinning many of the biochemical and physiological processes within cells. Allostery occurs when a binding event at one site on a protein affects binding at a remote functional site, allowing for the regulation of activity. Although protein allostery is a well-studied phenomenon, how allostery evolves remains one of the most intriguing questions in biology. In this research, we will use a well-studied allosteric protein to find out how allosteric regulation emerges in precursor proteins and how distant functional sites are coupled. This will be achieved by generating a library of chimeric proteins to study the potential transfer of allostery through the “grafting” of regulatory domains to proteins that naturally do not possess allosteric regulation. These chimeric proteins will subsequently undergo systematic mutagenesis to provide fundamental insights into how distant functional sites may “communicate” across long distances. Finally, the biological impact of newly acquired allostery on bacterial metabolism will be revealed using mass spectrometry-based metabolomics tools. This project will provide significant insights into the origins and evolution of allostery, unravelling strategies for the development of novel therapeutics and biosensors.