dc.contributor.author | Thapa, Chandan | |
dc.contributor.author | Roivas, Pekka | |
dc.contributor.author | Haataja, Tatu | |
dc.contributor.author | Permi, Perttu | |
dc.contributor.author | Pentikäinen, Ulla | |
dc.date.accessioned | 2021-03-31T11:23:14Z | |
dc.date.available | 2021-03-31T11:23:14Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Thapa, C., Roivas, P., Haataja, T., Permi, P., & Pentikäinen, U. (2021). The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A. <i>Frontiers in Molecular Biosciences</i>, <i>8</i>, Article 650881. <a href="https://doi.org/10.3389/fmolb.2021.650881" target="_blank">https://doi.org/10.3389/fmolb.2021.650881</a> | |
dc.identifier.other | CONVID_52623812 | |
dc.identifier.uri | https://jyx.jyu.fi/handle/123456789/74917 | |
dc.description.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. | en |
dc.format.mimetype | application/pdf | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Frontiers Media SA | |
dc.relation.ispartofseries | Frontiers in Molecular Biosciences | |
dc.rights | CC BY 4.0 | |
dc.subject.other | intrinsically disordered proteins | |
dc.subject.other | NMR spectroscopy | |
dc.subject.other | SAXS | |
dc.subject.other | PP2A | |
dc.subject.other | protein-protein interaction | |
dc.subject.other | PP2A inhibitor proteins | |
dc.title | The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A | |
dc.type | article | |
dc.identifier.urn | URN:NBN:fi:jyu-202103312249 | |
dc.contributor.laitos | Bio- ja ympäristötieteiden laitos | fi |
dc.contributor.laitos | Department of Biological and Environmental Science | en |
dc.contributor.oppiaine | Nanoscience Center | fi |
dc.contributor.oppiaine | Solu- ja molekyylibiologia | fi |
dc.contributor.oppiaine | Nanoscience Center | en |
dc.contributor.oppiaine | Cell and Molecular Biology | en |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | |
dc.type.coar | http://purl.org/coar/resource_type/c_2df8fbb1 | |
dc.description.reviewstatus | peerReviewed | |
dc.relation.issn | 2296-889X | |
dc.relation.volume | 8 | |
dc.type.version | publishedVersion | |
dc.rights.copyright | © 2021 Thapa, Roivas, Haataja, Permi and Pentikäinen | |
dc.rights.accesslevel | openAccess | fi |
dc.relation.grantnumber | 288235 | |
dc.relation.grantnumber | 283481 | |
dc.subject.yso | NMR-spektroskopia | |
dc.subject.yso | proteiinit | |
dc.subject.yso | syöpäsolut | |
dc.subject.yso | soluviestintä | |
dc.format.content | fulltext | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p26254 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p4332 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p23898 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p28740 | |
dc.rights.url | https://creativecommons.org/licenses/by/4.0/ | |
dc.relation.doi | 10.3389/fmolb.2021.650881 | |
dc.relation.funder | Research Council of Finland | en |
dc.relation.funder | Research Council of Finland | en |
dc.relation.funder | Suomen Akatemia | fi |
dc.relation.funder | Suomen Akatemia | fi |
jyx.fundingprogram | Academy Project, AoF | en |
jyx.fundingprogram | Research costs of Academy Research Fellow, AoF | en |
jyx.fundingprogram | Akatemiahanke, SA | fi |
jyx.fundingprogram | Akatemiatutkijan tutkimuskulut, SA | fi |
jyx.fundinginformation | This work was supported by Academy of Finland (283481 to UP, and 288235 to PP), and the University of Jyväskylä Graduate School (CT). | |
dc.type.okm | A1 | |