Cullin3 (Cul3), a key factor of protein ubiquitination, is able to interact with dozens of different proteins containing a BTB (Bric-a-brac, Tramtrack and Broad Complex) domain. We here targeted the Cul3-BTB interface by using the intriguing approach of stabilizing the α-helical conformation of Cul3-based peptides through the "stapling" with a hydrocarbon cross-linker. In particular, by combining theoretical and experimental techniques, we designed and characterized stapled Cul3-based peptides embedding the helix 2 of the protein (residues 49-68). Intriguingly, CD and NMR experiments demonstrate that these stapled peptides were able to adopt the helical structure that the fragment assumes in the parent protein. We also show that some of these peptides were able to bind to the BTB of the tetrameric KCTD11, a substrate adaptor involved in HDAC1 degradation, with high affinity (~ 300-600 nM). Cul3-derived staple peptides are also able to bind the BTB of the pentameric KCTD5. Interestingly

Cullin3-BTB interface: a novel target for stapled peptides / de Paola, I; Pirone, L; Palmieri, M; Balasco, N; Esposito, L; Russo, L; Mazzà, D; DI MARCOTULLIO, Lucia; Di Gaetano, S; Malgieri, G; Vitagliano, L; Pedone, E; Zaccaro, L.. - In: PLOS ONE. - ISSN 1932-6203. - STAMPA. - 10:4(2015). [10.1371/journal.pone.0121149]

Cullin3-BTB interface: a novel target for stapled peptides

DI MARCOTULLIO, LUCIA;
2015

Abstract

Cullin3 (Cul3), a key factor of protein ubiquitination, is able to interact with dozens of different proteins containing a BTB (Bric-a-brac, Tramtrack and Broad Complex) domain. We here targeted the Cul3-BTB interface by using the intriguing approach of stabilizing the α-helical conformation of Cul3-based peptides through the "stapling" with a hydrocarbon cross-linker. In particular, by combining theoretical and experimental techniques, we designed and characterized stapled Cul3-based peptides embedding the helix 2 of the protein (residues 49-68). Intriguingly, CD and NMR experiments demonstrate that these stapled peptides were able to adopt the helical structure that the fragment assumes in the parent protein. We also show that some of these peptides were able to bind to the BTB of the tetrameric KCTD11, a substrate adaptor involved in HDAC1 degradation, with high affinity (~ 300-600 nM). Cul3-derived staple peptides are also able to bind the BTB of the pentameric KCTD5. Interestingly
2015
cullin3; KCTD11; ubiquitylation
01 Pubblicazione su rivista::01a Articolo in rivista
Cullin3-BTB interface: a novel target for stapled peptides / de Paola, I; Pirone, L; Palmieri, M; Balasco, N; Esposito, L; Russo, L; Mazzà, D; DI MARCOTULLIO, Lucia; Di Gaetano, S; Malgieri, G; Vitagliano, L; Pedone, E; Zaccaro, L.. - In: PLOS ONE. - ISSN 1932-6203. - STAMPA. - 10:4(2015). [10.1371/journal.pone.0121149]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/783287
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