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PLoS Comput Biol. 2014 Feb 6;10(2):e1003443. doi: 10.1371/journal.pcbi.1003443. eCollection 2014 Feb.

Compact modeling of allosteric multisite proteins: application to a cell size checkpoint.

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Department of Mathematics, Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, United States of America.
Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
Computational and Applied Mathematics Department, Rice University, Houston, Texas, United States of America.


We explore a framework to model the dose response of allosteric multisite phosphorylation proteins using a single auxiliary variable. This reduction can closely replicate the steady state behavior of detailed multisite systems such as the Monod-Wyman-Changeux allosteric model or rule-based models. Optimal ultrasensitivity is obtained when the activation of an allosteric protein by its individual sites is concerted and redundant. The reduction makes this framework useful for modeling and analyzing biochemical systems in practical applications, where several multisite proteins may interact simultaneously. As an application we analyze a newly discovered checkpoint signaling pathway in budding yeast, which has been proposed to measure cell growth by monitoring signals generated at sites of plasma membrane growth. We show that the known components of this pathway can form a robust hysteretic switch. In particular, this system incorporates a signal proportional to bud growth or size, a mechanism to read the signal, and an all-or-none response triggered only when the signal reaches a threshold indicating that sufficient growth has occurred.

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