title: Compact modeling of allosteric multisite proteins: application to a cell size checkpoint.
abstract: 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.
authors: Department of Mathematics, Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, United States of America.
authors: Germán
authors: G
authors: Enciso
authors: Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
authors: Douglas R
authors: DR
authors: Kellogg
authors: Computational and Applied Mathematics Department, Rice University, Houston, Texas, United States of America.
authors: Arturo
authors: A
authors: Vargas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000495:Allosteric Site; D048708:Cell Growth Processes; D019295:Computational Biology; D008954:Models, Biological; D008958:Models, Molecular; D010766:Phosphorylation; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; C101740:ZDS1 protein, S cerevisiae; C490702:PKC1 protein, S cerevisiae; D011493:Protein Kinase C; D054648:Protein Phosphatase 2; C051302:RHO1 protein, S cerevisiae; D020741:rho GTP-Binding Proteins