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Science. 2020 Feb 28;367(6481):1039-1042. doi: 10.1126/science.aay5359.

Polymerization in the actin ATPase clan regulates hexokinase activity in yeast.

Author information

1
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
2
Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
3
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
4
Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
5
School of Biological Sciences, University of Bristol, Bristol BS8 1TQ, UK.
6
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. awm@mcb.harvard.edu egarner@g.harvard.edu.

Abstract

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 Saccharomyces cerevisiae 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.

PMID:
32108112
DOI:
10.1126/science.aay5359

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