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Issue 7, 2013
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Regulation of proteinprotein binding by coupling between phosphorylation and intrinsic disorder: analysis of human protein complexes

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Abstract

Phosphorylation offers a dynamic way to regulate protein activity, subcellular localization, and stability. The majority of signaling pathways involve an extensive set of proteinprotein interactions, and phosphorylation is widely used to regulate proteinprotein binding by affecting the stability, kinetics and specificity of interactions. Previously it was found that phosphorylation sites tend to be located on proteinprotein binding interfaces and may orthosterically modulate the strength of interactions. Here we studied the effect of phosphorylation on protein binding in relation to intrinsic disorder for different types of human protein complexes with known structure of the binding interface. Our results suggest that the processes of phosphorylation, binding and disorder–order transitions are coupled to each other, with about one quarter of all disordered interface Ser/Thr/Tyr sites being phosphorylated. Namely, residue site disorder and interfacial states significantly affect the phosphorylation of serine and to a lesser extent of threonine. Tyrosine phosphorylation might not be directly associated with binding through disorder, and is often observed in ordered interface regions which are not predicted to be disordered in the unbound state. We analyze possible mechanisms of how phosphorylation might regulate proteinprotein binding via intrinsic disorder, and specifically focus on how phosphorylation could prevent disorder–order transitions upon binding.

Graphical abstract: Regulation of protein–protein binding by coupling between phosphorylation and intrinsic disorder: analysis of human protein complexes

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Publication details

The article was received on 11 Nov 2012, accepted on 08 Jan 2013 and first published on 11 Jan 2013


Article type: Paper
DOI: 10.1039/C3MB25514J
Citation: Mol. BioSyst., 2013,9, 1620-1626
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    Regulation of proteinprotein binding by coupling between phosphorylation and intrinsic disorder: analysis of human protein complexes

    H. Nishi, J. H. Fong, C. Chang, S. A. Teichmann and A. R. Panchenko, Mol. BioSyst., 2013, 9, 1620
    DOI: 10.1039/C3MB25514J

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