What’s in an Average? An Ensemble View of Phosphorylation Effects Alexander F. Chin, Vincent J. Hilser  Structure  Volume 25, Issue 4, Pages 573-575 (April 2017) DOI: 10.1016/j.str.2017.03.012 Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 1 An Ensemble Framework of Post-Translational Modification Unifies Behavior of both Structured and Disordered Protein Systems (A) Single structural view of phosphorylation effects, where each phosphorylation state is adequately represented as a single structure. (B) Phosphorylation can modulate order-to-disorder transitions, wherein one of the conformations is not unique. The structured conformation may include a partner binding site absent in the disordered conformation. (C) Ensemble view of phosphorylation. Before phosphorylation, a disordered protein exists as a heterogeneous ensemble of disordered states, in which individual states may have varying dimensions and binding properties. (D) After phosphorylation, a disordered protein can continue to exist as an ensemble of disordered states, but phosphorylation may selectively enhance the probability of certain disordered states with specific properties. In this illustration, phosphorylation increases the overall population of disordered but more compact molecules that have a binding site for ligand (square box). (E) Measured properties are actually probability weighted averages over all states in the ensemble. In cases wherein a single structure dominates (A), the observed average accurately captures the component states. As systems move down the dynamic continuum (B–D), the average provides less insight into the individual states. (F) Apparent rigid-body conformational change in structured proteins, disorder-to-order transitions, and disordered heterogeneous ensemble re-distribution may not be discreet regimes, but rather conceptual points on a smooth continuum of increasing disorder. The ensemble model unifies experimental results from systems along all points of this continuum. Structure 2017 25, 573-575DOI: (10.1016/j.str.2017.03.012) Copyright © 2017 Elsevier Ltd Terms and Conditions