Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Structural and Functional Evolution of Proteins by Conformational Diversity

Protein evolution has most commonly been studied either theoretically, by analyzing the sequence of the protein (1, 2), or experimentally, by resurrecting ancestral proteins in the lab and performing ligand binding studies to determine function. Thus far, structural and dynamic evolution have largely been left out of molecular evolution studies. Here we incorporate both structure and dynamics to elucidate the molecular principles behind the divergence in the evolutionary path of the steroid receptor proteins. We begin by determining the likely structure of three evolutionary diverged, ancestral steroid receptor proteins(1) using the Zipping and Assembly Method with FRODA (ZAMF)(2). Our predictions are within 1.9Å RMSD of the crystal structure of ancestral corticoid steroid receptor. Beyond comparing static structure prediction, the main advantage of ZAMF is that it allows us to observe protein dynamics. Therefore we can investigate differences in the diverged proteins’ available dynamic space. Strikingly, our dynamics analysis of these predicted structures indicates that evolutionary diverged proteins do not share the same dynamic subspace. Moreover, our dynamic analysis enables us to identify critical mutations that most affect dynamics, therefore it shows the critical mutations leading to a divergence in function, which are verified experimentally.

  1. P. Anbazhagan, M. Purushottam, H. B. K. Kumar, O. Mukherjee, S. Jain, R. Sowdhamini, J Biomol Struct Dyn 27, 581-598 (2009).
  2. Z. Liu, Y. Zu, L. Wu, S. Zhang, J Biomol Struct Dyn 28, 97-106 (2010)
  3. J.T. Bridgham, E.A. Ortlund, J. W. Thornton Nature 461, 515-519 (2009).
  4. Glembo, T. J. and Ozkan S.B., Biophys J. 98, 1046-1054 (2010).

T. J. Glembo1
S.B. Ozkan1

1Center for Biological Physics Department of Physics Arizona State University Tempe, AZ

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