Polymerization in the actin ATPase clan regulates hexokinase activity in yeast.
Publication Type:Journal Article
Source:Science, Volume 367, Issue 6481, p.1039-1042 (2020)
Keywords:Actins, Adenosine Triphosphatases, Glucokinase, Hexokinase, Polymerization, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
<p>The actin fold is found in cytoskeletal polymers, chaperones, and various metabolic enzymes. Many actin-fold proteins, such as the carbohydrate kinases, do not polymerize. We found that Glk1, a glucokinase, forms two-stranded filaments with ultrastructure that is distinct from that of cytoskeletal polymers. In cells, Glk1 polymerized upon sugar addition and depolymerized upon sugar withdrawal. Polymerization inhibits enzymatic activity; the Glk1 monomer-polymer equilibrium sets a maximum rate of glucose phosphorylation regardless of Glk1 concentration. A mutation that eliminated Glk1 polymerization alleviated concentration-dependent enzyme inhibition. Yeast containing nonpolymerizing Glk1 were less fit when growing on sugars and more likely to die when refed glucose. Glk1 polymerization arose independently from other actin-related filaments and may allow yeast to rapidly modulate glucokinase activity as nutrient availability changes.</p>