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Independent evolution of polymerization in the Actin ATPase clan regulates hexokinase activity

bioRxiv, ISSN: 2692-8205
2019
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  • Citations
    2
    • Citation Indexes
      2
      • CrossRef
        2

Article Description

The actin protein fold is found in cytoskeletal polymers, chaperones, and various metabolic enzymes. Many actin-fold proteins, like the carbohydrate kinases, do not polymerize. We find that Glk1, a Saccharomyces cerevisiae glucokinase, forms two-stranded filaments with unique ultrastructure, distinct from that of cytoskeletal polymers. In cells, Glk1 polymerizes upon sugar addition and depolymerizes upon sugar withdrawal. Glk1 polymerization inhibits its enzymatic activity, thus the Glk1 monomer-polymer equilibrium sets a maximum rate of glucose phosphorylation regardless of Glk1 concentration. A mutation eliminating Glk1 polymerization alleviates concentration-dependent enzyme inhibition, causing glucokinase activity to become unconstrained. Polymerization-based regulation of Glk1 activity serves an important function in vivo: yeast containing non-polymerizing Glk1 are less fit when growing on sugars and more likely to die when refed glucose. Glucokinase polymerization arose within the ascomycete fungi and is conserved across a group of divergent (150-200 mya) yeast. We show that Glk1 polymerization arose independently from other actin-related filaments and allows yeast to rapidly modulate glucokinase activity as nutrient availability changes.Yeast glucokinase activity is limited by its polymerization, which is critical for cell viability during glucose refeeding.

Bibliographic Details

Stoddard, Patrick R; Lynch, Eric M.; Farrell, Daniel P.; Justman, Quincey A.; Dosey, Annie M.; DiMaio, Frank; Williams, Tom A.; Kollman, Justin M.; Murray, Andrew W.; Garner, Ethan C.

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

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