Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)
The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A
Julkaisun tekijät: Thapa Chanda, Roivas Peikka, Haataja Tatu, Permi Perttu, Pentikainen Ulla
Kustantaja: FRONTIERS MEDIA SA
Paikka: Lausanne
Julkaisuvuosi: 2021
Journal: Frontiers in Molecular Biosciences
Tietokannassa oleva lehden nimi: FRONTIERS IN MOLECULAR BIOSCIENCES
Lehden akronyymi: FRONT MOL BIOSCI
Artikkelin numero: ARTN 650881
Volyymi: 8
Sivujen määrä: 16
eISSN: 2296-889X
DOI: http://dx.doi.org/10.3389/fmolb.2021.650881
Verkko-osoite: https://doi.org/10.3389/fmolb.2021.650881
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/57557884
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
