Long range recognition and selection in IDPs: The interactions of the C-terminus of p53
Kannan, S Lane, D.P Verma, C.S
Kannan, S
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Abstract
The C-terminal domain of p53 is an extensively studied IDP, interacting with different partners through multiple distinct conformations. To explore the interplay between preformed structural elements and intrinsic fluctuations in its folding and binding we combine extensive atomistic equilibrium and non-equilibrium simulations. We find that the free peptide segment rapidly interconverts between ordered and disordered states with significant populations of the conformations that are seen in the complexed states. The underlying global folding-binding landscape points to a synergistic mechanism in which recognition is dictated via long range electrostatic recognition which results in the formation of reactive structures as far away as 10 Å, and binding proceeds with the steering of selected conformations followed by induced folding at the target surface or within a close range.
Keywords
cyclin A, intrinsically disordered protein, protein binding, protein p53, protein S100B, S100B protein, human, sirtuin, amino acid sequence, binding site, chemistry, human, molecular dynamics, protein domain, protein folding, static electricity, thermodynamics, Amino Acid Sequence, Binding Sites, Cyclin A, Humans, Intrinsically Disordered Proteins, Molecular Dynamics Simulation, Protein Binding, Protein Folding, Protein Interaction Domains and Motifs, S100 Calcium Binding Protein beta Subunit, Sirtuins, Static Electricity, Thermodynamics, Tumor Suppressor Protein p53
Source Title
Scientific Reports
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Series/Report No.
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Attribution 4.0 International
Date
2016
DOI
10.1038/srep23750
Type
Article