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Intrinsically disordered proteins and conformational noise Implications in cancer

Mahmoudabadi, Gita and Rajagopalan, Krithika and Getzenberg, Robert H and Hannenhalli, Sridhar and Rangarajan, Govindan and Kulkarni, Prakash (2013) Intrinsically disordered proteins and conformational noise Implications in cancer. In: CELL CYCLE, 12 (1). pp. 26-31.

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Official URL: http://dx.doi.org/10.4161/cc.23178


Intrinsically disordered proteins, IDPs, are proteins that lack a rigid 3D structure under physiological conditions, at least in vitro. Despite the lack of structure, IDPs play important roles in biological processes and transition from disorder to order upon binding to their targets. With multiple conformational states and rapid conformational dynamics, they engage in myriad and often ``promiscuous'' interactions. These stochastic interactions between IDPs and their partners, defined here as conformational noise, is an inherent characteristic of IDP interactions. The collective effect of conformational noise is an ensemble of protein network configurations, from which the most suitable can be explored in response to perturbations, conferring protein networks with remarkable flexibility and resilience. Moreover, the ubiquitous presence of IDPs as transcriptional factors and, more generally, as hubs in protein networks, is indicative of their role in propagation of transcriptional (genetic) noise. As effectors of transcriptional and conformational noise, IDPs rewire protein networks and unmask latent interactions in response to perturbations. Thus, noise-driven activation of latent pathways could underlie state-switching events such as cellular transformation in cancer. To test this hypothesis, we created a model of a protein network with the topological characteristics of a cancer protein network and tested its response to a perturbation in presence of IDP hubs and conformational noise. Because numerous IDPs are found to be epigenetic modifiers and chromatin remodelers, we hypothesize that they could further channel noise into stable, heritable genotypic changes.

Item Type: Journal Article
Publication: CELL CYCLE
Additional Information: Copyright for this article belongs to LANDES BIOSCIENCE,USA
Keywords: intrinsically disordered proteins;noise;protein-protein interaction network;state-switching;cancer;evolution
Department/Centre: Division of Biological Sciences > Centre for Neuroscience
Division of Physical & Mathematical Sciences > Mathematics
Date Deposited: 20 Feb 2013 08:34
Last Modified: 20 Feb 2013 08:43
URI: http://eprints.iisc.ac.in/id/eprint/45821

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