Issue 4, 2011

Conformational selection or induced fit for Brinker and DNA recognition

Abstract

Brinker is the key target protein of the Drosophila Decapentaplegic morphogen signalling pathway. Brinker is widely expressed and can bind with DNA. NMR spectra suggest that apo-Brinker is intrinsically unstructured and undergoes a folding transition upon DNA-binding. However, the coupled mechanism of binding and folding is poorly understood. Here, we performed molecular dynamics (MD) simulations for both bound and apo-Brinker to study the mechanism. Room-temperature MD simulations suggest that Brinker becomes more rigid and stable upon DNA-binding. Kinetic analysis of high-temperature MD simulations shows that both bound and apo-Brinker unfold via a two-state process. The time scale of tertiary unfolding is significantly different between bound and apo-Brinker. The predicted Φ-values suggest that there are more residues with native-like transition state ensembles (TSEs) for bound Brinker than for apo-Brinker. The average RMSD differences between bound and apo-Brinker and Kolmogorov-Smirnov (KS) test analysis illustrate that Brinker folding upon DNA-binding might obey induced-fit mechanism based on MD simulations. These methods can be used for the research of other biomolecular folding upon ligand-binding.

Graphical abstract: Conformational selection or induced fit for Brinker and DNA recognition

Supplementary files

Article information

Article type
Paper
Submitted
27 May 2010
Accepted
05 Oct 2010
First published
18 Nov 2010

Phys. Chem. Chem. Phys., 2011,13, 1407-1412

Conformational selection or induced fit for Brinker and DNA recognition

F. Qin, Y. Jiang, Y. Chen, M. Wu, G. Yan, W. Ye, Y. Li, J. Zhang and H. Chen, Phys. Chem. Chem. Phys., 2011, 13, 1407 DOI: 10.1039/C0CP00701C

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