Abstract
The NUDIX
enzymes are involved in cellular metabolism and homeostasis, as well as
mRNA processing. Although highly conserved throughout all organisms,
their biological roles and biochemical redundancies remain largely
unclear. To address this, we globally resolve their individual
properties and inter-relationships. We purify 18 of the human NUDIX
proteins and screen 52 substrates, providing a substrate redundancy
map. Using crystal structures, we generate sequence alignment analyses
revealing four major structural classes. To a certain extent, their
substrate preference redundancies correlate with structural classes,
thus linking structure and activity relationships. To elucidate
interdependence among the NUDIX
hydrolases, we pairwise deplete them generating an epistatic
interaction map, evaluate cell cycle perturbations upon knockdown in
normal and cancer cells, and analyse their protein and mRNA expression
in normal and cancer tissues. Using a novel FUSION algorithm, we
integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.
- PMID:
- 29142246
- PMCID:
- PMC5688067
- DOI:
- 10.1038/s41467-017-01642-w
- [Indexed for MEDLINE]
FIGURE
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688067/figure/Fig1/
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