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Is catalytic activity of chaperones a selectable trait for the emergence of heat shock response?
Çetinbas, Murat; Shakhnovich, Eugene I.
Afiliação
  • Çetinbas M; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
  • Shakhnovich EI; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts. Electronic address: shakhnovich@chemistry.harvard.edu.
Biophys J ; 108(2): 438-48, 2015 Jan 20.
Article em En | MEDLINE | ID: mdl-25606691
Although heat shock response is ubiquitous in bacterial cells, the underlying physical chemistry behind heat shock response remains poorly understood. To study the response of cell populations to heat shock we employ a physics-based ab initio model of living cells where protein biophysics (i.e., folding and protein-protein interactions in crowded cellular environments) and important aspects of proteins homeostasis are coupled with realistic population dynamics simulations. By postulating a genotype-phenotype relationship we define a cell division rate in terms of functional concentrations of proteins and protein complexes, whose Boltzmann stabilities of folding and strengths of their functional interactions are exactly evaluated from their sequence information. We compare and contrast evolutionary dynamics for two models of chaperon action. In the active model, foldase chaperones function as nonequilibrium machines to accelerate the rate of protein folding. In the passive model, holdase chaperones form reversible complexes with proteins in their misfolded conformations to maintain their solubility. We find that only cells expressing foldase chaperones are capable of genuine heat shock response to the increase in the amount of unfolded proteins at elevated temperatures. In response to heat shock, cells' limited resources are redistributed differently for active and passive models. For the active model, foldase chaperones are overexpressed at the expense of downregulation of high abundance proteins, whereas for the passive model; cells react to heat shock by downregulating their high abundance proteins, as their low abundance proteins are upregulated.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Seleção Genética / Proteínas de Bactérias / Chaperoninas / Resposta ao Choque Térmico Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Seleção Genética / Proteínas de Bactérias / Chaperoninas / Resposta ao Choque Térmico Idioma: En Ano de publicação: 2015 Tipo de documento: Article