ATP shifts BRAF dimer interfaces inducing monomer inactive form 1433 acts as scaffold stabilizing BRAF even in the presence of ATP Scientific Achievement The mechanisms that affect the regulation of cell growth in certain tumor cells were revealed by a Genentech study of enzyme structures ID: 1033200
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1. Research DetailsCrystallography was performed on complexes containing BRAF (growth-signaling enzyme), ATP (driver of biological processes), and 14-3-3 (scaffolding protein).ATP shifts BRAF dimer interfaces, inducing monomer (inactive) form.14-3-3 acts as scaffold, stabilizing BRAF even in the presence of ATP.Scientific AchievementThe mechanisms that affect the regulation of cell growth in certain tumor cells were revealed by a Genentech study of enzyme structures, conducted in part at the Advanced Light Source (ALS).Significance and ImpactThe work establishes a framework for the rational discovery of new therapeutics to improve upon currently existing treatments.Publication about this research: N.P.D. Liau, T.J. Wendorff, J.G. Quinn, M. Steffek, W. Phung, P. Liu, J. Tang, F.J. Irudayanathan, S. Izadi, A.S. Shaw, S. Malek, S.G. Hymowitz, and J. Sudhamsu, Nat. Struct. Mol. Biol. 27, 134 (2020). Work was performed at Lawrence Berkeley National Laboratory, ALS Beamline 5.0.2, and Stanford Synchrotron Radiation Laboratory, Beamline 12-2. Operation of the ALS is supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences program.On-Off Switch for Regulating Tumor-Cell GrowthProtein crystallography studies of this enzyme (BRAF) revealed how structural changes induced by the presence of adenosine triphosphate (ATP) play a key role in turning cell growth on and off and how mutations initiate growth signals.