The glycolytic enzyme phosphofructokinase-1 assembles into filaments.
Bradley A WebbAnne M DoseyTorsten WittmannJustin M KollmanDiane L BarberPublished in: The Journal of cell biology (2017)
Despite abundant knowledge of the regulation and biochemistry of glycolytic enzymes, we have limited understanding on how they are spatially organized in the cell. Emerging evidence indicates that nonglycolytic metabolic enzymes regulating diverse pathways can assemble into polymers. We now show tetramer- and substrate-dependent filament assembly by phosphofructokinase-1 (PFK1), which is considered the "gatekeeper" of glycolysis because it catalyzes the step committing glucose to breakdown. Recombinant liver PFK1 (PFKL) isoform, but not platelet PFK1 (PFKP) or muscle PFK1 (PFKM) isoforms, assembles into filaments. Negative-stain electron micrographs reveal that filaments are apolar and made of stacked tetramers oriented with exposed catalytic sites positioned along the edge of the polymer. Electron micrographs and biochemical data with a PFKL/PFKP chimera indicate that the PFKL regulatory domain mediates filament assembly. Quantified live-cell imaging shows dynamic properties of localized PFKL puncta that are enriched at the plasma membrane. These findings reveal a new behavior of a key glycolytic enzyme with insights on spatial organization and isoform-specific glucose metabolism in cells.
Keyphrases
- single cell
- induced apoptosis
- genome wide
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- high resolution
- electronic health record
- transcription factor
- solar cells
- big data
- oxidative stress
- stem cells
- blood glucose
- endoplasmic reticulum stress
- dna methylation
- gene expression
- type diabetes
- bone marrow
- cell proliferation
- signaling pathway
- machine learning
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- mass spectrometry
- metabolic syndrome
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