Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Mechanism of Protein Evolution: Conformational Dynamics and Allostery
The first crystal structure was solved in late 1950, which revolutionized our ability to understand protein function. However, much more revolutionary information came after, when we learned that proteins dynamically interconvert between conformations in the native state. Indeed, the critical role of protein dynamics has become well recognized in various biological functions, including allosteric signaling and protein ligand recognition electron transfer . Likewise in protein evolution, the classical view of the one sequence-one structure-one function paradigm (the Pauling and Landsteiner proposal) is now being extended to a new view: an ensemble of conformations in equilibrium that can evolve new functions. Therefore, understanding inherent structural dynamics are crucial to obtain a more complete picture of protein evolution. A small local structural change due to a single mutation can lead to a large difference in conformational dynamics, even at quite distant residues due to allostery. We have recently analyzed conformational dynamics evolution of different protein families including GFP proteins(Kim et al 2015), beta-lactamase inhibitors (Zou et. al. 2014), and nuclear receptors and observed that alteration of conformational dynamics through allosteric regulations leads to functional changes. Moreover, proteome-wide conformational dynamics analysis of over 100 human proteins shows a strong correlations between dynamic profile, and corresponding evolutionary rate of each position(Gerek et al, 2013). Indeed, the preservation of dynamic properties of residues in a protein structure is critical for maintaining the biological function at a proteome scale.
Kim H. , Zou T. , Modi C. , Dorner K. , Grunkmeyer T. J., Chen L. , Fromme R. , Matz M. V., Ozkan S.B., and Wachter R.M. A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins. Structure 23, 34-43
Gerek Z.N., Kumar S. and Ozkan S. B. (2013) Structural dynamics flexibility informs function and evolution at a proteome scale Evol Appl. 6:4223-4332.
Center for Biological Physics