Our laboratory has recently introduced the term morpheeins to describe homo-oligomeric proteins that can exist as a dynamic equilibrium of structurally and functionally distinct quaternary assemblies. Morpheeins have been described as one possible structural basis for allosteric regulation of protein function. The key distinction between classic models of allosteric regulation and the morpheein model for allosteric regulation is the requirement for an oligomeric dissociation / change / reassociation event for the latter. It is possible that morpheeins are widespread but have gone undetected because of pervasive biases about the stability of protein quaternary structure assemblies. The prototype morpheein ensemble is porphobilinogen synthase, an enzyme that catalyzes an ancient and fundamental step in tetrapyrrole (e.g. heme and chlorophyll) biosynthesis. The porphobilinogen synthase family of enzymes has experienced a unique phylogenetic diversity in the use of metal ions for catalytic and allosteric function, and in the use of different morpheeins for control of protein function. The methods we use to investigate morpheeins are biochemical, biophysical, and kinetic.
