Electrostatically accelerated encounter and folding for facile recognition of intrinsically disordered proteins

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dc.contributor.author Ganguly, Debabani
dc.contributor.author Zhang, Weihong
dc.contributor.author Chen, Jianhan
dc.date.accessioned 2014-01-17T17:19:21Z
dc.date.available 2014-01-17T17:19:21Z
dc.date.issued 2013-11-23
dc.identifier.uri http://hdl.handle.net/2097/17046
dc.description.abstract Achieving facile specific recognition is essential for intrinsically disordered proteins (IDPs) that are involved in cellular signaling and regulation. Consideration of the physical time scales of protein folding and diffusion-limited protein-protein encounter has suggested that the frequent requirement of protein folding for specific IDP recognition could lead to kinetic bottlenecks. How IDPs overcome such potential kinetic bottlenecks to viably function in signaling and regulation in general is poorly understood. Our recent computational and experimental study of cell-cycle regulator p27 (Ganguly et al., J. Mol. Biol. (2012)) demonstrated that long-range electrostatic forces exerted on enriched charges of IDPs could accelerate protein-protein encounter via “electrostatic steering” and at the same time promote “folding-competent” encounter topologies to enhance the efficiency of IDP folding upon encounter. Here, we further investigated the coupled binding and folding mechanisms and the roles of electrostatic forces in the formation of three IDP complexes with more complex folded topologies. The surface electrostatic potentials of these complexes lack prominent features like those observed for the p27/Cdk2/cyclin A complex to directly suggest the ability of electrostatic forces to facilitate folding upon encounter. Nonetheless, similar electrostatically accelerated encounter and folding mechanisms were consistently predicted for all three complexes using topology-based coarse-grained simulations. Together with our previous analysis of charge distributions in known IDP complexes, our results support a prevalent role of electrostatic interactions in promoting efficient coupled binding and folding for facile specific recognition. These results also suggest that there is likely a co-evolution of IDP folded topology, charge characteristics, and coupled binding and folding mechanisms, driven at least partially by the need to achieve fast association kinetics for cellular signaling and regulation. en_US
dc.language.iso en_US en_US
dc.relation.uri http://doi.org/10.1371/journal.pcbi.1003363 en_US
dc.rights Attribution 3.0 Unported (CC BY 3.0)
dc.rights.uri https://creativecommons.org/licenses/by/3.0/
dc.subject Intrinsically disordered proteins en_US
dc.subject Protein folding en_US
dc.title Electrostatically accelerated encounter and folding for facile recognition of intrinsically disordered proteins en_US
dc.type Article (publisher version) en_US
dc.date.published 2013 en_US
dc.citation.doi 10.1371/journal.pcbi.1003363 en_US
dc.citation.issue 11 en_US
dc.citation.jtitle PLoS Computational Biology en_US
dc.citation.spage e1003363 en_US
dc.citation.volume 9 en_US
dc.contributor.authoreid jianhanc en_US


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Attribution 3.0 Unported (CC BY 3.0) Except where otherwise noted, the use of this item is bound by the following: Attribution 3.0 Unported (CC BY 3.0)

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