Direct Observation of the Dynamic Process Underlying Allosteric Signal Transmission

• DOI: 10.1021/ja809947w
• Publication Date: 2009-02-09T20:49:44Z
• Authors: Sven Brüschweiler; Paul Schanda; Karin Kloiber; Bernhard Brutscher; Georg Kontaxis; Robert Konrat; Martin Tollinger
• Keywords: Cooperativity; CREB-binding protein; Cooperative binding; Allosteric enzyme; Conformational isomerism

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