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Sci Rep. 2016 Mar 31;6:23750. doi: 10.1038/srep23750.

Long range recognition and selection in IDPs: the interactions of the C-terminus of p53.

Author information

1
Bioinformatics Institute (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671.
2
p53 Laboratory (A*STAR), 8A Biomedical Grove, #06-04/05, Neuros/Immunos, Singapore 138648.
3
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
4
Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543.

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.

PMID:
27030593
PMCID:
PMC4814905
DOI:
10.1038/srep23750
[Indexed for MEDLINE]
Free PMC Article
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