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Structure of the Pho85-Pho80 CDK-cyclin complex of the phosphate-responsive signal transduction pathway.

Molecular cell | Nov 30, 2007

http://www.ncbi.nlm.nih.gov/pubmed/18042456

The ability to sense and respond appropriately to environmental changes is a primary requirement of all living organisms. In response to phosphate limitation, Saccharomyces cerevisiae induces transcription of a set of genes involved in the regulation of phosphate acquisition from the ambient environment. A signal transduction pathway (the PHO pathway) mediates this response, with Pho85-Pho80 playing a vital role. Here we report the X-ray structure of Pho85-Pho80, a prototypic structure of a CDK-cyclin complex functioning in transcriptional regulation in response to environmental changes. The structure revealed a specific salt link between a Pho85 arginine and a Pho80 aspartate that makes phosphorylation of the Pho85 activation loop dispensable and that maintains a Pho80 loop conformation for possible substrate recognition. It further showed two sites on the Pho80 cyclin for high-affinity binding of the transcription factor substrate (Pho4) and the CDK inhibitor (Pho81) that are markedly distant to each other and the active site.

Pubmed ID: 18042456 RIS Download

Mesh terms: Binding Sites | Crystallography, X-Ray | Cyclin-Dependent Kinases | Cyclins | DNA-Binding Proteins | Enzyme Activation | Enzyme Inhibitors | Models, Molecular | Mutant Proteins | Phenylalanine | Phosphates | Phosphorylation | Protein Binding | Protein Structure, Secondary | Repressor Proteins | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Signal Transduction | Structure-Activity Relationship | Substrate Specificity | Transcription Factors

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM051377
  • Agency: NIGMS NIH HHS, Id: GM068826
  • Agency: NIGMS NIH HHS, Id: R01 GM051377
  • Agency: NIGMS NIH HHS, Id: R01 GM051377-14
  • Agency: NIGMS NIH HHS, Id: R01 GM068826
  • Agency: NIGMS NIH HHS, Id: R01 GM068826-04

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