{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:07:33Z","timestamp":1791410853234,"version":"4.3.3"},"reference-count":53,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2014,9,8]],"date-time":"2014-09-08T00:00:00Z","timestamp":1410134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2014,10]]},"abstract":"The regulation of P<\/jats:styled-content>lasmodium\u00a0falciparum<\/jats:italic> protein phosphatase type\u00a01 (PfPP1) activity remains to be deciphered. Data from homologous eukaryotic type\u00a01 protein phosphatases (PP1) suggest that several protein regulators should be involved in this essential process. One such regulator, named PfI2 based on its primary sequence homology with eukaryotic inhibitor\u00a02 (I2), was recently shown to be able to interact with PfPP1 and to inhibit its phosphatase activity, mainly through the canonical \u2018RVxF\u2019 binding motif. The details of the structural and functional characteristics of this interaction are investigated here. Using NMR spectroscopy, a second site of interaction is suggested to reside between residues D94 and T117 and contains the \u2018FxxR\/KxR\/K\u2019 binding motif present in other I2 proteins. This site seems to play in concert\/synergy with the \u2018RVxF\u2019 motif to bind PP1, because only mutations in both motifs were able to abolish this interaction completely. However, regarding the structure\/function relationship, mutation of either the \u2018RVxF\u2019 or \u2018FxxR\/KxR\/K\u2019 motif is more drastic, because each mutation prevents the capacity of PfI2 to trigger germinal vesicle breakdown in microinjected X<\/jats:styled-content>enopus<\/jats:italic> oocytes. This indicates that the tight association of the PfI2 regulator to PP1, mediated by a two\u2010site interaction, is necessary to exert its function. Based on these results, the use of a peptide derived from the \u2018FxxR\/KxR\/K\u2019 PfI2 motif was investigated for its potential effect on P<\/jats:styled-content>lasmodium<\/jats:italic> growth. This peptide, fused at its N\u2010terminus to a penetrating sequence, was shown to accumulate specifically in infected erythrocytes and to have an antiplasmodial effect.<\/jats:p><\/jats:sec>Structured digital abstract<\/jats:title>\n\n\nPfPP1<\/jats:ext-link> and PfI2<\/jats:ext-link> bind<\/jats:ext-link> by nuclear magnetic resonance<\/jats:ext-link> (1<\/jats:ext-link>, 2<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n\nPP1<\/jats:ext-link>\u00a0physically interacts<\/jats:ext-link> with PfPP1<\/jats:ext-link> by anti tag coimmunoprecipitation<\/jats:ext-link> (View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n\nPfI2<\/jats:ext-link>\u00a0binds<\/jats:ext-link> to PfPP1<\/jats:ext-link> by enzyme linked immunosorbent assay<\/jats:ext-link> (View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n\nPfI2<\/jats:ext-link>\u00a0binds<\/jats:ext-link> to PfPP1<\/jats:ext-link> by surface plasmon resonance<\/jats:ext-link> (1<\/jats:ext-link>, 2<\/jats:ext-link>, 3<\/jats:ext-link>, 4<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/febs.12960","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T13:53:25Z","timestamp":1407851605000},"page":"4519-4534","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Identification of a Plasmodium\u00a0falciparum<\/i> inhibitor\u20102 motif involved in the binding and regulation activity of protein phosphatase type\u00a01"],"prefix":"10.1111","volume":"281","author":[{"given":"Aline","family":"Fr\u00e9ville","sequence":"first","affiliation":[{"name":"Center for Infection and Immunity of Lille Inserm U1019\u2010CNRS UMR 8204 Universit\u00e9 Lille Nord de France Institut Pasteur de Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9raldine","family":"Tellier","sequence":"additional","affiliation":[{"name":"Center for 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