Unknown

Dataset Information

0

The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A.


ABSTRACT: Protein phosphatase 2A (PP2A) activity is critical for maintaining normal physiological cellular functions. PP2A is inhibited by endogenous inhibitor proteins in several pathological conditions including cancer. A PP2A inhibitor protein, ARPP-19, has recently been connected to several human cancer types. Accordingly, the knowledge about ARPP-19-PP2A inhibition mechanism is crucial for the understanding the disease development and the therapeutic targeting of ARPP-19-PP2A. Here, we show the first structural characterization of ARPP-19, and its splice variant ARPP-16 using NMR spectroscopy, and SAXS. The results reveal that both ARPP proteins are intrinsically disordered but contain transient secondary structure elements. The interaction mechanism of ARPP-16/19 with PP2A was investigated using microscale thermophoresis and NMR spectroscopy. Our results suggest that ARPP-PP2A A-subunit interaction is mediated by linear motif and has modest affinity whereas, the interaction of ARPPs with B56-subunit is weak and transient. Like many IDPs, ARPPs are promiscuous binders that transiently interact with PP2A A- and B56 subunits using multiple interaction motifs. In summary, our results provide a good starting point for future studies and development of therapeutics that block ARPP-PP2A interactions.

SUBMITTER: Thapa C 

PROVIDER: S-EPMC8032985 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC9250585 | biostudies-literature
| S-EPMC6043496 | biostudies-literature
| S-EPMC8204386 | biostudies-literature
| S-EPMC5419745 | biostudies-literature
| S-EPMC8887652 | biostudies-literature
| S-EPMC2956375 | biostudies-other
| S-EPMC7462833 | biostudies-literature
| S-EPMC6699704 | biostudies-literature
| S-EPMC4534220 | biostudies-literature
| S-EPMC3949125 | biostudies-literature