Thousands of different proteins are known, spanning the whole of the biological world, that contain haem as an integral component. Haemoproteins are responsible for binding and transportation of gaseous molecules, biochemical catalysis, and redox reactions in the electron-transport chain. Haem itself is a simple organo-transition-metal compound containing iron at the centre of a porphyrin macrocycle. By providing a metal centre for gas binding, substrate binding and charge transfer, haem is pivotal to the biochemical function of a haemoprotein. Traditionally, haem’s role was considered to be confined to haemoproteins with specific binding pockets, where it is a tightly bound and essential prosthetic group. Emerging evidence has dramatically shifted this view, revealing that haem also exists in an exchangeable pool within cells capable of transiently binding to a wider range of proteins, including those not classically defined as haemoproteins. cell.[1, 2]
We have been investigating how haem interacts with circadian-clock proteins in ways that impact their ability to form protein–protein or protein–DNA complexes. Specifically, we have been using NMR, fluorescence lifetime and correlation spectroscopy and light scattering techniques. In parallel, we have performed cellular assays to identify changes in circadian rhythmicity caused by excesses and deficiencies in haem.