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Article: Biochemical and Structural Characterization of an Intramolecular Interaction in FOXO3a and Its Binding with p53

TitleBiochemical and Structural Characterization of an Intramolecular Interaction in FOXO3a and Its Binding with p53
Authors
Keywordsapoptosis
p53
intramolecular interaction
NMR
FOXO3a
Issue Date2008
Citation
Journal of Molecular Biology, 2008, v. 384, n. 3, p. 590-603 How to Cite?
Abstract© 2008 FOXO3a, a forkhead (FH) transcription factor and member of the FH box class O (FOXO) subfamily, has been shown to promote the translocation of p53 to the cytoplasm, thereby inducing the mitochondria-associated apoptotic pathway. However, the binding sites that mediate this interaction between FOXO3a and p53 have not been identified. Here, we show that two regions within FOXO3a, the FH–DNA binding domain and a conserved C-terminal transactivation domain (CR3), interact with the DNA binding domain of p53, with affinities in the low millimolar range and low micromolar range, respectively. Our data further suggest that within the FOXO3a molecule, the FH and CR3 domains engage in an intramolecular interaction with low micromolar affinity. Moreover, we used NMR to determine the solution structure of the FH domain. This enabled us to map the binding site for the CR3, which overlaps with the DNA binding site. We demonstrate that an intrinsically disordered linker between the FH and CR3 domains is required for full p53 binding activity. We also show that p53 disrupts the intramolecular interaction between FH and CR3. These results provide evidence for interplay of the FH and CR3 domains in association with p53.
Persistent Identifierhttp://hdl.handle.net/10722/292927
ISSN
2020 Impact Factor: 5.469
2020 SCImago Journal Rankings: 3.189
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Feng-
dc.contributor.authorMarshall, Christopher B.-
dc.contributor.authorYamamoto, Kazuo-
dc.contributor.authorLi, Guang Yao-
dc.contributor.authorPlevin, Michael J.-
dc.contributor.authorYou, Han-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorIkura, Mitsuhiko-
dc.date.accessioned2020-11-17T14:57:31Z-
dc.date.available2020-11-17T14:57:31Z-
dc.date.issued2008-
dc.identifier.citationJournal of Molecular Biology, 2008, v. 384, n. 3, p. 590-603-
dc.identifier.issn0022-2836-
dc.identifier.urihttp://hdl.handle.net/10722/292927-
dc.description.abstract© 2008 FOXO3a, a forkhead (FH) transcription factor and member of the FH box class O (FOXO) subfamily, has been shown to promote the translocation of p53 to the cytoplasm, thereby inducing the mitochondria-associated apoptotic pathway. However, the binding sites that mediate this interaction between FOXO3a and p53 have not been identified. Here, we show that two regions within FOXO3a, the FH–DNA binding domain and a conserved C-terminal transactivation domain (CR3), interact with the DNA binding domain of p53, with affinities in the low millimolar range and low micromolar range, respectively. Our data further suggest that within the FOXO3a molecule, the FH and CR3 domains engage in an intramolecular interaction with low micromolar affinity. Moreover, we used NMR to determine the solution structure of the FH domain. This enabled us to map the binding site for the CR3, which overlaps with the DNA binding site. We demonstrate that an intrinsically disordered linker between the FH and CR3 domains is required for full p53 binding activity. We also show that p53 disrupts the intramolecular interaction between FH and CR3. These results provide evidence for interplay of the FH and CR3 domains in association with p53.-
dc.languageeng-
dc.relation.ispartofJournal of Molecular Biology-
dc.subjectapoptosis-
dc.subjectp53-
dc.subjectintramolecular interaction-
dc.subjectNMR-
dc.subjectFOXO3a-
dc.titleBiochemical and Structural Characterization of an Intramolecular Interaction in FOXO3a and Its Binding with p53-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jmb.2008.09.025-
dc.identifier.scopuseid_2-s2.0-84954358441-
dc.identifier.volume384-
dc.identifier.issue3-
dc.identifier.spage590-
dc.identifier.epage603-
dc.identifier.eissn1089-8638-
dc.identifier.isiWOS:000261711300004-
dc.identifier.issnl0022-2836-

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