Figure 4.

Hypothesized model for the purinosome as a liquid condensate regulated by molecular chaperones. Inactive forms of FGAMS and PPAT are recruited to chaperoning complexes, where they are folded into their active state to promote transient interactions with GART to form the purinosome core. These associations promote the recruitment of the other enzymes into purinosome condensates localized at microtubule–mitochondrion interfaces. Complete purinosome condensates are hypothesized to be responsible for the channeled conversion of PRPP into GMP or AMP (blue dashed line). Disruption of HSP90 activity through STA9090 was shown to perturb the properties of purinosome condensates and result in FGAMS-only assemblies. FGAMS, formylglycinamidine ribonucleotide synthase; GART, glycinamide ribonucleotide transformylase; HSP90, heat shock protein 90 kDa; PPAT, phosphoribosyl pyrophosphate amidotransferase; PRPP, phosphoribosyl pyrophosphate.