|
|
ReportsCrystal Structure of an Ancient Protein: Evolution by Conformational Epistasis
The structural mechanisms by which proteins have evolved new functions are known only indirectly. We report x-ray crystal structures of a resurrected ancestral protein—the
1 Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA. * These authors contributed equally to this work.
The editors suggest the following Related Resources on Science sites:In Science Magazine
In Science Signaling
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
|
450 million-year-old precursor of vertebrate glucocorticoid (GR) and mineralocorticoid (MR) receptors. Using structural, phylogenetic, and functional analysis, we identify the specific set of historical mutations that recapitulate the evolution of GR's hormone specificity from an MR-like ancestor. These substitutions repositioned crucial residues to create new receptor-ligand and intraprotein contacts. Strong epistatic interactions occur because one substitution changes the conformational position of another site. "Permissive" mutations—substitutions of no immediate consequence, which stabilize specific elements of the protein and allow it to tolerate subsequent function-switching changes—played a major role in determining GR's evolutionary trajectory. 
To whom correspondence should be addressed. E-mail: 
Magazine | News | Signaling | Careers | Multimedia | Collections | Help | Site Map | RSS
Subscribe | Feedback | Privacy / Legal | About Us | Advertise With Us | Contact Us
© 2007 American Association for the Advancement of Science. All Rights Reserved.
AAAS is a partner of HINARI, AGORA, PatientInform, CrossRef, and COUNTER.
You have reached the bottom of the page. Back to top