Theory Lunch: Eileen Jaffe


Friday, April 28, 2017, 12:00pm to 2:00pm


WAB 563

Title: Morpheeins, the transformers of allostery

Eileen Jaffe

Department of Medical Genetics and Molecular Biology, Lewis Katz School of Medicine, Temple University


About 15 years ago, we stumbled upon a disease-associated missense variant of an essential human enzyme that had unexpected kinetic and biophysical properties. Through the next decade we determined that this enzyme exists as an equilibrium among architecturally distinct assemblies. The interconversion between the assemblies forms a physiologically relevant basis for allosteric regulation. More surprisingly, the multimers must dissociate, change shape, and reassemble as part of the allosteric process. Thus arose the definition of the morpheein model of protein allostery, illustrated pictorially below:

A key lesson remains how this discovery could easily have been overlooked as experimental artifact based on the "one sequence, one structure, one function" dogma that continues to predominate our analysis of the growing protein sequence and protein crystal structure databases. The effect of reversible multimerization equilibria between properly folded, but alternately assembled proteins has long been overlooked as another of Nature's tricks to optimize functional diversity from a limited genome. In the well characterized examples, the conformational change in the dissociated state is a hinge motion between two folded domains of each subunit.

Location: Warren Alpert 563

Theory Lunch website