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Verfasst von:Neitz, Hermann [VerfasserIn]   i
 Paul, Niels Benjamin [VerfasserIn]   i
 Häge, Florian [VerfasserIn]   i
 Lindner, Christina [VerfasserIn]   i
 Graebner, Roman [VerfasserIn]   i
 Kovermann, Michael [VerfasserIn]   i
 Thomas, Franziska [VerfasserIn]   i
Titel:Identification of novel functional mini-receptors by combinatorial screening of split-WW domains
Verf.angabe:Hermann Neitz, Niels Benjamin Paul, Florian R. Häge, Christina Lindner, Roman Graebner, Michael Kovermann and Franziska Thomas
E-Jahr:2022
Jahr:14 Jul 2022
Umfang:12 S.
Fussnoten:Gesehen am 13.02.2023
Titel Quelle:Enthalten in: Chemical science
Ort Quelle:Cambridge : RSC, 2010
Jahr Quelle:2022
Band/Heft Quelle:13(2022), 31, Seite 9079-9090
ISSN Quelle:2041-6539
Abstract:β-Sheet motifs such as the WW domain are increasingly being explored as building blocks for synthetic biological applications. Since the sequence-structure relationships of β-sheet motifs are generally complex compared to the well-studied α-helical coiled coil (CC), other approaches such as combinatorial screening should be included to vary the function of the peptide. In this study, we present a combinatorial approach to identify novel functional mini-proteins based on the WW-domain scaffold, which takes advantage of the successful reconstitution of the fragmented WW domain of hPin1 (hPin1WW) by CC association. Fragmentation of hPin1WW was performed in both loop 1 (CC-hPin1WW-L1) and loop 2 (CC-hPin1WW-L2), and the respective fragments were linked to the strands of an antiparallel heterodimeric CC. Structural analysis by CD and NMR spectroscopy revealed structural reconstitution of the WW-domain scaffold only in CC-hPin1WW-L1, but not in CC-hPin1WW-L2. Furthermore, by using 1H-15N HSQC NMR, fluorescence and CD spectroscopy, we demonstrated that binding properties of fragmented hPin1WW in CC-hPin1WW-L1 were fully restored by CC association. To demonstrate the power of this approach as a combinatorial screening platform, we synthesized a four-by-six library of N- and C-terminal hPin1WW-CC peptide fragments that was screened for a WW domain that preferentially binds to ATP over cAMP, phophocholine, or IP6. Using this screening platform, we identified one WW domain, which specifically binds ATP, and a phosphorylcholine-specific WW-based mini-receptor, both having binding dissociation constants in the lower micromolar range.
DOI:doi:10.1039/D2SC01078J
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1039/D2SC01078J
 kostenfrei: Volltext: https://pubs.rsc.org/en/content/articlelanding/2022/sc/d2sc01078j
 DOI: https://doi.org/10.1039/D2SC01078J
Datenträger:Online-Ressource
Sprache:eng
Bibliogr. Hinweis:Forschungsdaten: Thomas, Franziska, 1980 - : Identification of novel functional mini-receptors by combinatorial screening of split-WW domains [research data]
K10plus-PPN:1834593573
Verknüpfungen:→ Zeitschrift

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