IP₇-SPX Domain Interaction Controls Fungal Virulence by Stabilizing Phosphate Signaling Machinery.

ABSTRACT: In the human-pathogenic fungus Cryptococcus neoformans, the inositol polyphosphate signaling pathway is critical for virulence. We recently demonstrated the key role of the inositol pyrophosphate IP₇ (isomer 5-PP-IP₅) in driving fungal virulence; however, the mechanism of action remains elusive. Using genetic and biochemical approaches, and mouse infection models, we show that IP₇ synthesized by Kcs1 regulates fungal virulence by binding to a conserved lysine surface cluster in the SPX domain of Pho81. Pho81 is the cyclin-dependent kinase (CDK) inhibitor of the phosphate signaling (PHO) pathway. We also provide novel mechanistic insight into the role of IP₇ in PHO pathway regulation by demonstrating that IP₇ functions as an inte

SUBMITTER: Desmarini D 

PROVIDER: S-EPMC7587432 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature