Allostery is the structural manifestation of information transduction in biomolecules. Its hallmark is conformational change induced by perturbations at a distal site. An increasing body of evidence demonstrates the presence of allostery in very flexible and even disordered proteins, encouraging a thermodynamic description of this phenomenon. Still, resolving such processes at atomic resolution is difficult. Here we establish a protocol to determine atomistic thermodynamic models of such systems using high-resolution solution state nuclear magnetic resonance data and extensive molecular simulations. Using this methodology, we study information transduction in the WW domain of a key cell-cycle regulator Pin1. Pin1 binds promiscuously to phospho-Ser/Thr-Pro motifs, however, disparate structural and dynamic responses have been reported upon binding different ligands. Our model consists of two topologically distinct states whose relative population may be specifically skewed by an incoming ligand. This model provides a canonical basis for the understanding of multi-functionality in Pin1.
Copyright © 2016 Elsevier Ltd. All rights reserved.