Phosphorylation Rheostat

Science's STKE  05 Jul 2005:
Vol. 2005, Issue 291, pp. tw245
DOI: 10.1126/stke.2912005tw245

Modulation of the activity of proteins by phosphorylation has often been described as a binary switch, but Pufall et al. show that finer rheostat-like control can also be achieved. The transcription factor Ets-1 exhibits a graded DNA binding affinity that depends on the number of sites that are phosphorylated. Ets-1 exists in conformational equilibrium between a dynamic conformation that binds DNA and a well-folded inhibited state. Increasing phosphorylation progressively shifts the equilibrium toward the inhibited state and thus fine-tunes the level of activity. The phosphorylated region, which serves as the allosteric effector, is predominantly unstructured and flexible and probably acts through transient interactions.

M. A. Pufall, G. M. Lee, M. L. Nelson, H.-S. Kang, A. Velyvis, L. E. Kay, L. P. McIntosh, B. J. Graves, Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region. Science 309, 142-145 (2005). [Abstract] [Full Text]