Berlin 2005 – wissenschaftliches Programm
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SYBN: Biological and Social Networks
SYBN 3: Biologische und Soziale Netzwerke, Postersitzung
SYBN 3.18: Poster
Montag, 7. März 2005, 14:00–15:30, Poster TU E
Nonlinear Protein Degradation and the Function of Genetic Circuits — •Ulrich Gerland1, Nicolas Buchler2, and Terence Hwa3 — 1Department Physik and CENS, LMU München, Germany — 2Center for Studies in Physics and Biology, The Rockefeller University, New York — 3Physics Department and Center for Theoretical Biological Physics, University of California at San Diego
The functions of genetic circuits require a sufficient degree of cooperativity in the circuit components. In this study, we examine a simple source of cooperativity that stems from the nonlinear degradation of multimeric proteins. Ample experimental evidence suggests that protein subunits degrade less rapidly when associated in multimeric complexes, an effect we refer to as ‘cooperative stabilization’. For homodimers, this effect leads to a concentration dependence in the protein degradation rate, since monomers which are predominant at low protein concentrations are more rapidly degraded. For such proteins, cooperative stabilization can effectively widen the accessible range of protein levels in vivo. Such an increased range is important both for the robust operation of genetic circuits as well as their evolvability. Through theoretical analysis of two model gene circuits in bacteria, we show that a few-fold difference between the degradation rate of monomers and dimers can substantially enhance the operation of these circuits. Our results suggest that cooperative stabilization needs to be considered explicitly and characterized quantitatively in any systematic experimental or theoretical study of gene circuits.