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TitlePolymerization in the actin ATPase clan regulates hexokinase activity in yeast.
Journal, issue, pagesScience, Vol. 367, Issue 6481, Page 1039-1042, Year 2020
Publish dateFeb 28, 2020
AuthorsPatrick R Stoddard / Eric M Lynch / Daniel P Farrell / Annie M Dosey / Frank DiMaio / Tom A Williams / Justin M Kollman / Andrew W Murray / Ethan C Garner /
PubMed AbstractThe 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 ...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.
External linksScience / PubMed:32108112 / PubMed Central
MethodsEM (helical sym.) / X-ray diffraction
Resolution3.59 - 3.8 Å
Structure data

20309

6pdt

EMDB-20309, PDB-6pdt:
cryoEM structure of yeast glucokinase filament
Method: EM (helical sym.) / Resolution: 3.8 Å

PDB-6p4x:
Crystal Structure of the S. cerevisiae glucokinase, Glk1
Method: X-RAY DIFFRACTION / Resolution: 3.59 Å

Chemicals

ChemComp-PO4:
PHOSPHATE ION / Phosphate

ChemComp-GLC:
alpha-D-glucopyranose / Glucose

ChemComp-MG:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

Source
  • Saccharomyces cerevisiae (brewer's yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
KeywordsTRANSFERASE / hexokinase / actin atpase / glycolysis / filament

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