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Direct observation of the dynamic process underlying allosteric signal transmission. | LitMetric

Direct observation of the dynamic process underlying allosteric signal transmission.

J Am Chem Soc

Department of Computational & Structural Biology, Max F. Perutz Laboratories, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Published: March 2009

AI Article Synopsis

Article Abstract

Allosteric regulation is an effective mechanism of control in biological processes. In allosteric proteins a signal originating at one site in the molecule is communicated through the protein structure to trigger a specific response at a remote site. Using NMR relaxation dispersion techniques we directly observe the dynamic process through which the KIX domain of CREB binding protein communicates allosteric information between binding sites. KIX mediates cooperativity between pairs of transcription factors through binding to two distinct interaction surfaces in an allosteric manner. We show that binding the activation domain of the mixed lineage leukemia (MLL) transcription factor to KIX induces a redistribution of the relative populations of KIX conformations toward a high-energy state in which the allosterically activated second binding site is already preformed, consistent with the Monod-Wyman-Changeux (WMC) model of allostery. The structural rearrangement process that links the two conformers and by which allosteric information is communicated occurs with a time constant of 3 ms at 27 degrees C. Our dynamic NMR data reveal that an evolutionarily conserved network of hydrophobic amino acids constitutes the pathway through which information is transmitted.

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Source
http://dx.doi.org/10.1021/ja809947wDOI Listing

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