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Abstract
Order-disorder Continuum in Protein Function and Disease
According to the “positional information paradigm”, if natural selection is acting to preserve a biological function, changes in the protein sequence that alter that function will be removed from the population over evolutionary time. If allowed to implicate stabilizing selection for the evolution of disordered regions as we do for the folded domains, then the concept of my presentation is as follows: neither disordered regions nor structured domains are independent of one another, but sense and respond to each other and have co-evolved to have some synergistic properties that are required to enable key biological functions. I will focus on the intimate relationship between CK1 and DVL proteins, a kinase-substrate affair that controls WNT signal transduction in development and homeostasis. Our mechanistic data highlight a continuum of structural states that bridges two highly different dynamic regimes and regulates protein function. Disturbing the thin line between structure and disorder may result in disease phenotypes of animal models.
