Evolution of Protein Structure and Function in the Steroid Hormone Receptors

Ancestral protein reconstruction – or APR – allows hypotheses about the functions of ancient proteins to be tested experimentally.  But that is only the beginning.  We have used APR as platforms for elucidating in detail the evolutionary, genetic, and biophysical mechanisms by which ancient proteins evolved their modern functions.  Specifically, we genetically manipulate reconstructed proteins to recapitulate the evolutionary process and then study the  molecular functions, atomic structures, and biophysical behaviors of proteins as they evolved through time.  We have gained some insight into how the biophysical architecture of ancient proteins shaped their evolution and how the architecture of modern proteins reflects their histories.  I will report on studies using APR to understand the diversification of function in the steroid receptors, a group of hormone-regulated transcription factors of extraordinary biological and medical importance in humans and other animals.