Structure of the Pho85-Pho80 CDK-cyclin complex of the phosphate-responsive signal transduction pathway.
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.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Kexin
K
Huang
Ian
I
Ferrin-O'Connell
Wei
W
Zhang
Gordon A
GA
Leonard
Erin K
EK
O'Shea
Florante A
FA
Quiocho
D001665:Binding Sites; D018360:Crystallography, X-Ray; D018844:Cyclin-Dependent Kinases / Q000737:chemistry*; D016213:Cyclins / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry; D010649:Phenylalanine; D010710:Phosphates / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism
D016213:Cyclins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050505:Mutant Proteins; C060292:PHO4 protein, S cerevisiae; C066824:PHO80 protein, S cerevisiae; C081227:PHO81 protein, S cerevisiae; D010710:Phosphates; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D010649:Phenylalanine; D018844:Cyclin-Dependent Kinases; C058605:PHO85 protein, S cerevisiae