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Design and structure determination of a composite zinc finger containing a nonpeptide foldamer helical domain.

dc.rights.licenseopenen_US
dc.contributor.authorLOMBARDO, Caterina Maria
hal.structure.identifierARNA - Acides Nucléiques : Régulations Naturelle et Artificielle
dc.contributor.authorVASANTHA KUMAR, M. V
dc.contributor.authorDOUAT, Céline
hal.structure.identifierInstitut Européen de Chimie et de Biologie
dc.contributor.authorROSU, Frédéric
hal.structure.identifierARNA - Acides Nucléiques : Régulations Naturelle et Artificielle
dc.contributor.authorMERGNY, Jean-Louis
hal.structure.identifierARNA - Acides Nucléiques : Régulations Naturelle et Artificielle
dc.contributor.authorSALGADO, Gilmar F.
dc.contributor.authorGUICHARD, Gilles
IDREF: 084339268
dc.date.accessioned2019
dc.date.available2019
dc.date.issued2019
dc.identifier.issn1520-5126en_US
dc.identifier.other10.1021/jacs.8b12240en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/3799
dc.description.abstractEnA number of foldamer back bones have been described as useful mimics of protein secondary structure elements,enabling for example the design of synthetic oligomers with the ability to engage specific protein surfaces. Synthetic folded backbones can also be used to create artificial proteins in which a folded peptide segment (e.g., an α -helix, a loop) is replaced by its unnatural counterpart, with the expectation that the resulting molecule would maintain its ability to fold while manifesting new exploitable features. The similarities in screw sense, pitch, and polarity between peptide α -helices and oligourea 2.5-helices suggest that a tertiary structure could be retained when swapping the two backbones in a protein sequence. In the present work, we move a step toward the creation of such composite proteins by replacing the 10-residue long original α-helical segment in the Cys2His2 zinc finger 3 of transcription factor Egr1 (also known as Zif268) by an oligourea sequence bearing two appropriately spaced imidazole side chains for zinc coordination. We show by spectroscopic techniques and mass spectrometry analysis under native conditions that the ability of the peptide/oligourea hybrid to coordinate the zinc ion is not affected by the foldamer replacement. Moreover, detailed NMR analysis provides evidence that the engineered zinc finger motif adopts a folded structure in which the native β-sheet arrangement of the peptide region and global arrangement of DNA-binding side chains arepreserved. Titration in the presence of the Egr1 target DNA sequence supports binding to GC bases as reported for the wild-type zinc finger.
dc.language.isoENen_US
dc.subjectManufacturing process
dc.subjectinformation model
dc.subjectSTEP
dc.title.enDesign and structure determination of a composite zinc finger containing a nonpeptide foldamer helical domain.
dc.typeArticle de revueen_US
dc.identifier.doi10.1021/jacs.8b12240
dc.subject.halSciences de l'environnement/Ingénierie de l'environnementen_US
dc.subject.halSciences de l'Homme et Société/Sciences de l'information et de la communicationen_US
dc.subject.halSciences de l'ingénieur [physics]/Mécanique [physics.med-ph]/Génie mécanique [physics.class-ph]en_US
bordeaux.journalJournal of the American Chemical Societyen_US
bordeaux.page2516-2525en_US
bordeaux.volume141en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248
bordeaux.issue6en_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03181429
hal.version1
hal.date.transferred2021-03-29T12:56:27Z
hal.exporttrue
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