Expanding the Concepts in Protein Structure-Function Relationships and Enzyme Kinetics: Teaching using Morpheeins.

A morpheein is a homo-oligomeric protein that can exist as an ensemble of physiologically significant and functionally different alternate quaternary assemblies. Morpheeins exist in nature and utilize conformational equilibria between different tertiary structures to form distinct oligomers as a means of regulating their function. Notably, alternate morpheeins are not misfolded forms of a protein; they are differently assembled native states that contain alternate subunit conformations. Transitions between alternate morpheein assemblies involve oligomer dissociation, conformational change in the dissociated state, and reassembly to a different oligomer. These transitions occur in response to the protein's environment, e.g., effector molecules, and represent a new model of allosteric regulation. The unique features of morpheeins are being revealed through detailed characterization of the prototype enzyme, porphobilinogen synthase, which exists in a dynamic equilibrium of a high activity octamer, a low activity hexamer, and two dimer conformations. Morpheeins are likely far more common than previously appreciated. There are, however, both intellectual and experimental barriers to recognizing proteins as morpheeins. These barriers derive from the way we were taught and continue to teach about protein folding, protein purification, protein structure-function relationships, and enzyme kinetics. This article explores some of these limitations and encourages incorporation of morpheeins into both introductory and advanced biochemistry classes.