Structural Analysis of the CDK-Cyclin Complex of Pho85-Pho80 and Genome-Wide Characterization of the Phosphate Starvation Response in Schizosaccharomyces pombe
Contributors: O'Shea, Erin K.; Murray, Andrew; D'Souza, Victoria; Gaudet, Rachelle; Denic, Vlad
Published: 2012
Language: eng
Description: Inorganic phosphate is an essential nutrient required by all organisms for optimal growth. During phosphate starvation, Saccharomyces cerevisiae induces a set of genes responsible for the regulation of inorganic phosphate acquisition. The phosphate-responsive signaling (PHO) pathway controls this response, with the CDK-cyclin complex Pho85-Pho80 playing a prominent role. Here we report the X-ray structure of the Pho85-Pho80 complex, identifying the unique structural features that distinguish it from other cell cycle associated CDK-cyclin complexes. The structure reveals a specific salt bridge between a Pho85 arginine and a Pho80 aspartate that maintains a Pho80 loop confirmation important for substrate recognition and makes phosphorylation of the Pho85 activation loop dispensible. We show that a cluster of residues distal to the kinase active site are involved in a high affinity interaction between the Pho80 cyclin and the transcription factor substrate (Pho4). The structure also reveals a separate high affinity binding site for the CDK inhibitor (Pho81).
Notes: Keywords: PHO Pathway, S. pombe, Whole-Genome.

Thesis Ph.D. Harvard University 2012