Direct interaction between intrinsically disordered proteins is often difficult to be characterized hampering the elucidation of their binding mechanism. Particularly challenging are the cases of extreme fuzziness of the complex, which is now appearing as a common interaction mode,requiring new models for their description.1
So far, nuclear magnetic resonance spectroscopy has proven to be one of the most powerful techniques to characterize at atomic level intrinsically disordered proteins and their interactions, including those cases where the formed complexes are highly dynamics.2
Here we present the characterization of the interaction between a viral protein, the Early region 1A protein from Adenovirus,3 and a disordered region of the human CREB-binding protein, namely the fourth intrinsically disordered linker CBP-ID4.4
E1A has been widely studied as a prototypical viral oncogene. Its interaction with folded domains of CBP has been mapped before, proving its functional interaction with this transcriptional factor.5 However, the role of the linkers of CBP in this interaction has never been investigated before.
1 M. Fuxreiter, P. Tompa, 2012, Advances in Experimental Medicine and Biology, vol 725. Springer, New York, NY.
2 a) S. Contreras-Martos et al., Sci Rep. 2017, 7(1),4676 ; b) A. Borgia, K. Bugge et al. Nature, 2018, 555(7694):61-66. c) R. Schneider et al. Curr Opin Struct Biol. 2018, 54,10-18.
3 T. Hosek et al. Chem. Eur. J. 2016, 22, 13010–13013.
4 A. Piai et al. Biophys. J. 2016, 110, 372–381.
5 a)J. C. Ferreon et al. Proc.Natl.Acad.Sci.USA 2009, 106, 13260-13265;b) P. Haberz et al. Protein Sci., 2016, 25,2256-2257.