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.
Huang
Kexin
K
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Ferrin-O'Connell
Ian
I
Zhang
Wei
W
Leonard
Gordon A
GA
O'Shea
Erin K
EK
Quiocho
Florante A
FA
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