Berlin 2012 – scientific programme

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BP: Fachverband Biologische Physik

BP 29: Posters: Regulation

BP 29.4: Poster

Thursday, March 29, 2012, 17:30–19:30, Poster A

Reversible Enzyme Regulation as a Source of Bistability in Covalent Protein Modification Systems — •Ronny Straube and Carsten Conradi — Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany

Goldbeter and Koshland have shown that covalent protein modifications can generate highly sigmoidal response behavior (known as ultrasensitivity) when the converter enzymes (e.g. kinase and phosphatase) operate in saturation [1]. However, in vivo, the converter enzymes are often themselves subject to regulation, e.g. by an allosteric effector or by additional covalent modifications. As a result, they typically exist in inter convertible states of high and low activity which may compete for substrate. Here, we show that this competition is structurally sufficient to generate a bistable system response already at the level of a single protein modification cycle, i.e. without the requirement for multisite modifications or additional positive feedback loops. In contrast to mechanisms based on multisite modifications bistability is even predicted to occur when substrate molecules and enzymes are present in equal amounts. Our results provide an alternative and challenging view on the origin of bistability in the Cdk1-Cdc25-Wee1 system [2] which governs the M-phase transition of the cell cycle in fission yeast.

[1] Goldbeter A, Koshland, DE Jr. An amplified sensitivity arising from covalent modification in biological systems. Proc. Natl. Acad. Sci USA 78, 6840-6844 (1981). [2] Ferrell JE Jr. Feedback regulation of opposing enzymes generates robust, all-or-none bistable responses. Curr. Biol. 18, R244 (2008).