3 research outputs found
Potassium Starvation in Yeast: Mechanisms of Homeostasis Revealed by Mathematical Modeling
The intrinsic ability of cells to adapt to a wide range of environmental conditions is a fundamental process required for survival. Potassium is the most abundant cation in living cells and is required for essential cellular processes, including the regulation of cell volume, pH and protein synthesis. Yeast cells can grow from low micromolar to molar potassium concentrations and utilize sophisticated control mechanisms to keep the internal potassium concentration in a viable range. We developed a mathematical model for Saccharomyces cerevisiae to explore the complex interplay between biophysical forces and molecular regulation facilitating potassium homeostasis. By using a novel inference method (“the reverse tracking algorithm”) we predicted and then verified experimentally that the main regulators under conditions of potassium starvation are proton fluxes responding to changes of potassium concentrations. In contrast to the prevailing view, we show that regulation of the main potassium transport systems (Trk1,2 and Nha1) in the plasma membrane is not sufficient to achieve homeostasis
Cooperativity and flexibility in enzyme evolution
Enzymes are flexible catalysts, and there has been substantial
discussion about the extent to which this flexibility contributes
to their catalytic efficiency. What has been significantly less
discussed is the extent to which this flexibility contributes to
their evolvability. Despite this, recent years have seen an
increasing number of both experimental and computational
studies that demonstrate that cooperativity and flexibility play
significant roles in enzyme innovation. This review covers key
developments in the field that emphasize the importance of
enzyme dynamics not just to the evolution of new enzyme
function(s), but also as a property that can be harnessed in the
design of new artificial enzymes.The European Research Council has provided financial support under the
European Community’s Seventh Framework Program (FP7/2007-2013)/ERC
Grant Agreement No. 306474. This work was also funded by the Feder
Funds, Grants from the Spanish Ministry of Economy and Competitiveness
(BIO2015-66426-R and CSD2009-00088) and the Human Frontier Science
Program (RGP0041/2017). A.P. is a Wenner-Gren Foundations Postdoctoral
Fellow and S. C. L. K. is a Wallenberg Academy Fellow